531 results on '"Anthony Watts"'
Search Results
2. Archaeal Lipids Regulating the Trimeric Structure Dynamics of Bacteriorhodopsin for Efficient Proton Release and Uptake
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Sijin Chen, Xiaoyan Ding, Chao Sun, Fei Wang, Xiao He, Anthony Watts, and Xin Zhao
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bacteriorhodopsin ,archaeal lipids ,S-TGA-1 and PGP-Me ,lipid–protein interactions ,trimer stability ,proton release and uptake ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
S-TGA-1 and PGP-Me are native archaeal lipids associated with the bacteriorhodopsin (bR) trimer and contribute to protein stabilization and native dynamics for proton transfer. However, little is known about the underlying molecular mechanism of how these lipids regulate bR trimerization and efficient photocycling. Here, we explored the specific binding of S-TGA-1 and PGP-Me with the bR trimer and elucidated how specific interactions modulate the bR trimeric structure and proton release and uptake using long-term atomistic molecular dynamic simulations. Our results showed that S-TGA-1 and PGP-Me are essential for stabilizing the bR trimer and maintaining the coherent conformational dynamics necessary for proton transfer. The specific binding of S-TGA-1 with W80 and K129 regulates proton release on the extracellular surface by forming a “Glu-shared” model. The interaction of PGP-Me with K40 ensures proton uptake by accommodating the conformation of the helices to recruit enough water molecules on the cytoplasmic side. The present study results could fill in the theoretical gaps of studies on the functional role of archaeal lipids and could provide a reference for other membrane proteins containing similar archaeal lipids.
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- 2022
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3. Constraints on the Rheology of the Lithosphere From Flexure of the Pacific Plate at the Hawaiian Islands
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Ashley Bellas, Shijie Zhong, and Anthony Watts
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lithospheric rheology ,viscoelastic deformation ,geodynamic modeling ,Geophysics. Cosmic physics ,QC801-809 ,Geology ,QE1-996.5 - Abstract
Abstract The rheology of oceanic lithosphere is important to our understanding of mantle dynamics and to the emergence and manifestations of plate tectonics. Data from experimental rock mechanics suggest rheology is dominated by three different deformation mechanisms including frictional sliding, low‐temperature plasticity, and high‐temperature creep, from shallow depths at relatively cold temperatures to large depths at relatively high temperatures. However, low‐temperature plasticity is poorly understood. This study further constrains low‐temperature plasticity by comparing observations of flexure at the Hawaiian Islands to predictions from 3‐D viscoelastic loading models with a realistic lithospheric rheology of frictional sliding, low‐temperature plasticity, and high‐temperature creep. We find that previously untested flow laws significantly underpredict the amplitude and overpredict the wavelength of flexure at Hawaii. These flow laws can, however, reproduce observations if they are weakened by a modest reduction (25–40%) in the plastic activation energy. Lithospheric rheology is strongly temperature dependent, and so we explore uncertainties in the thermal structure with different conductive cooling models and convection simulations of plume‐lithosphere interactions. Convection simulations show that thermal erosion from a plume only perturbs the lithospheric temperature significantly at large depths so that when it is added to the thermal structure, it produces a small increase in deflection. In addition, defining the temperature profile by the cooling plate model produces only modest weakening relative to the cooling half‐space model. Therefore, variation of the thermal structure does not appear to be a viable means of bringing laboratory‐derived flow laws for low‐temperature plasticity into agreement with geophysical field observations and modeling.
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- 2020
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4. Dynamic tuneable G protein-coupled receptor monomer-dimer populations
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Patricia M. Dijkman, Oliver K. Castell, Alan D. Goddard, Juan C. Munoz-Garcia, Chris de Graaf, Mark I. Wallace, and Anthony Watts
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Science - Abstract
Evidence suggests oligomerisation of G protein-coupled receptors in membranes, but this is controversial. Here, authors use single-molecule and ensemble FRET, and spectroscopy to show that the neurotensin receptor 1 forms multiple dimer conformations that interconvert - “rolling” interfaces.
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- 2018
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5. Dynamic Coupling of Tyrosine 185 with the Bacteriorhodopsin Photocycle, as Revealed by Chemical Shifts, Assisted AF-QM/MM Calculations and Molecular Dynamic Simulations
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Sijin Chen, Xiaoyan Ding, Chao Sun, Anthony Watts, Xiao He, and Xin Zhao
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bacteriorhodopsin ,Tyrosine 185 ,retinal chromophore ,photo-intermediate and photocycle ,AF-QM/MM calculations and MD simulations ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Aromatic residues are highly conserved in microbial photoreceptors and play crucial roles in the dynamic regulation of receptor functions. However, little is known about the dynamic mechanism of the functional role of those highly conserved aromatic residues during the receptor photocycle. Tyrosine 185 (Y185) is a highly conserved aromatic residue within the retinal binding pocket of bacteriorhodopsin (bR). In this study, we explored the molecular mechanism of the dynamic coupling of Y185 with the bR photocycle by automated fragmentation quantum mechanics/molecular mechanics (AF-QM/MM) calculations and molecular dynamic (MD) simulations based on chemical shifts obtained by 2D solid-state NMR correlation experiments. We observed that Y185 plays a significant role in regulating the retinal cis–trans thermal equilibrium, stabilizing the pentagonal H-bond network, participating in the orientation switch of Schiff Base (SB) nitrogen, and opening the F42 gate by interacting with the retinal and several key residues along the proton translocation channel. Our findings provide a detailed molecular mechanism of the dynamic couplings of Y185 and the bR photocycle from a structural perspective. The method used in this paper may be applied to the study of other microbial photoreceptors.
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- 2021
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6. A new low-turbulence wind tunnel for animal and small vehicle flight experiments
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Daniel B. Quinn, Anthony Watts, Tony Nagle, and David Lentink
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biomechanics ,wind tunnel ,turbulence ,unmanned aerial vehicles ,flight stability ,gust mitigation ,Science - Abstract
Our understanding of animal flight benefits greatly from specialized wind tunnels designed for flying animals. Existing facilities can simulate laminar flow during straight, ascending and descending flight, as well as at different altitudes. However, the atmosphere in which animals fly is even more complex. Flow can be laminar and quiet at high altitudes but highly turbulent near the ground, and gusts can rapidly change wind speed. To study flight in both laminar and turbulent environments, a multi-purpose wind tunnel for studying animal and small vehicle flight was built at Stanford University. The tunnel is closed-circuit and can produce airspeeds up to 50 m s−1 in a rectangular test section that is 1.0 m wide, 0.82 m tall and 1.73 m long. Seamless honeycomb and screens in the airline together with a carefully designed contraction reduce centreline turbulence intensities to less than or equal to 0.030% at all operating speeds. A large diameter fan and specialized acoustic treatment allow the tunnel to operate at low noise levels of 76.4 dB at 20 m s−1. To simulate high turbulence, an active turbulence grid can increase turbulence intensities up to 45%. Finally, an open jet configuration enables stereo high-speed fluoroscopy for studying musculoskeletal control in turbulent flow.
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- 2017
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7. A comparative characterisation of commercially available lipid-polymer nanoparticles formed from model membranes
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Henry Sawczyc, Sabine Heit, and Anthony Watts
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Biophysics ,General Medicine - Abstract
From the discovery of the first membrane-interacting polymer, styrene maleic-acid (SMA), there has been a rapid development of membrane solubilising polymers. These new polymers can solubilise membranes under a wide range of conditions and produce varied sizes of nanoparticles, yet there has been a lack of broad comparison between the common polymer types and solubilising conditions. Here, we present a comparative study on the three most common commercial polymers: SMA 3:1, SMA 2:1, and DIBMA. Additionally, this work presents, for the first time, a comparative characterisation of polymethacrylate copolymer (PMA). Absorbance and dynamic light scattering measurements were used to evaluate solubilisation across key buffer conditions in a simple, adaptable assay format that looked at pH, salinity, and divalent cation concentration. Lipid-polymer nanoparticles formed from SMA variants were found to be the most susceptible to buffer effects, with nanoparticles from either zwitterionic DMPC or POPC:POPG (3:1) bilayers only forming in low to moderate salinity (
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- 2023
8. Two states of a light-sensitive membrane protein captured at room temperature using thin-film sample mounts
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Danny Axford, Peter J. Judge, Juan F. Bada Juarez, Tristan O. C. Kwan, James Birch, Javier Vinals, Anthony Watts, and Isabel Moraes
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polymer films ,Light ,Polymers ,archaerhodopsin ,Archaeal Proteins ,thin-film sample ,membrane proteins ,Crystallography, X-Ray ,Photoreceptors, Microbial ,retinal ,Retina ,Isomerism ,X-Ray Diffraction ,Structural Biology ,synchrotron ,Halorubrum ,X-Rays ,Temperature ,photoreceptors ,Proton Pumps ,Research Papers ,Lipids ,LCP ,proton transport ,room temperature ,lipidic cubic phase ,Crystallization ,microbial rhodopsin - Abstract
High-resolution X-ray diffraction data were collected at room temperature for light- and dark-adapted states of the archaerhodopsin-3 photoreceptor using transparent and opaque polymer-film sample mounts., Room-temperature diffraction methods are highly desirable for dynamic studies of biological macromolecules, since they allow high-resolution structural data to be collected as proteins undergo conformational changes. For crystals grown in lipidic cubic phase (LCP), an extruder is commonly used to pass a stream of microcrystals through the X-ray beam; however, the sample quantities required for this method may be difficult to produce for many membrane proteins. A more sample-efficient environment was created using two layers of low X-ray transmittance polymer films to mount crystals of the archaerhodopsin-3 (AR3) photoreceptor and room-temperature diffraction data were acquired. By using transparent and opaque polymer films, two structures, one corresponding to the desensitized, dark-adapted (DA) state and the other to the ground or light-adapted (LA) state, were solved to better than 1.9 Å resolution. All of the key structural features of AR3 were resolved, including the retinal chromophore, which is present as the 13-cis isomer in the DA state and as the all-trans isomer in the LA state. The film-sandwich sample environment enables diffraction data to be recorded at room temperature in both illuminated and dark conditions, which more closely approximate those in vivo. This simple approach is applicable to a wide range of membrane proteins crystallized in LCP and light-sensitive samples in general at synchrotron and laboratory X-ray sources.
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- 2022
9. Ultrafast Two-Dimensional Infrared Spectroscopy Resolved a Structured Lysine 159 on the Cytoplasmic Surface of the Microbial Photoreceptor Bacteriorhodopsin
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Rong Hu, Xiaoyan Ding, Pengyun Yu, Xuemei He, Anthony Watts, Xin Zhao, and Jianping Wang
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Colloid and Surface Chemistry ,Bacteriorhodopsins ,Lysine ,Spectrum Analysis ,General Chemistry ,Photoreceptors, Microbial ,Biochemistry ,Amides ,Catalysis - Abstract
Bacteriorhodopsin (bR) is a light-driven microbial receptor, and lysine 159 (K159) is a charged residue on the cytoplasmic (CP) side of its E-F loop. However, its conformation and function remain unknown due to fast surface dynamics. By utilizing a
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- 2022
10. Reconciling lithospheric rheology between laboratory experiments, field observations and different tectonic settings
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Anthony Watts, Shijie Zhong, and Ashley Bellas
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Tectonics ,Geophysics ,Field (physics) ,Rheology ,Geochemistry and Petrology ,Lithosphere ,Lithospheric flexure ,Geology - Abstract
SUMMARY Recent modelling studies have shown that laboratory-derived rheology is too strong to reproduce observations of flexure at the Hawaiian Islands, while the same rheology appears consistent with outer rise—trench flexure at circum-Pacific subduction zones. Collectively, these results indicate that the rheology of an oceanic plate boundary is stronger than that of its interior, which, if correct, presents a challenge to understanding the formation of trenches and subduction initiation. To understand this dilemma, we first investigate laboratory-derived rheology using fully dynamic viscoelastic loading models and find that it is too strong to reproduce the observationally inferred elastic thickness, Te, at most plate interior settings. The Te can, however, be explained if the yield stress of low-temperature plasticity is significantly reduced, for example, by reducing the activation energy from 320 kJ mol−1, as in Mei et al., to 190 kJ mol−1 as was required by previous studies of the Hawaiian Islands, implying that the lithosphere beneath Hawaii is not anomalous. Second, we test the accuracy of the modelling methods used to constrain the rheology of subducting lithosphere, including the yield stress envelope (YSE) method, and the broken elastic plate model (BEPM). We show the YSE method accurately reproduces the model Te to within ∼10 per cent error with only modest sensitivity to the assumed strain rate and curvature. Finally, we show that the response of a continuous plate is significantly enhanced when a free edge is introduced at or near an edge load, as in the BEPM, and is sensitive to the degree of viscous coupling at the free edge. Since subducting lithosphere is continuous and generally mechanically coupled to a sinking slab, the BEPM may falsely introduce a weakness and hence overestimate Te at a trench because of trade-off. This could explain the results of recent modelling studies that suggest the rheology of subducting oceanic plate is stronger than that of its interior. However, further studies using more advanced thermal and mechanical models will be required in the future in order to quantify this.
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- 2021
11. Translational Biophysics – 20th IUPAB Congress Session Commentary
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Jesús Pérez-Gil and Anthony Watts
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medicine.medical_specialty ,Structural Biology ,Commentary ,Biophysics ,medicine ,Medical physics ,Session (computer science) ,Psychology ,Molecular Biology - Published
- 2021
12. Lipid nanoparticle technologies for the study of G protein-coupled receptors in lipid environments
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Steven Lavington and Anthony Watts
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rHDL ,SMALP ,Chemistry ,Biophysics ,Membrane biology ,Nanoparticle ,Review ,Lipodisq ,Lipid-protein interactions ,Structural Biology ,lipids (amino acids, peptides, and proteins) ,G protein-coupled receptor ,Nanodisc ,Receptor ,Molecular Biology ,Integral membrane protein ,hormones, hormone substitutes, and hormone antagonists ,Function (biology) - Abstract
G protein-coupled receptors (GPCRs) are a large family of integral membrane proteins which conduct a wide range of biological roles and represent significant drug targets. Most biophysical and structural studies of GPCRs have been conducted on detergent-solubilised receptors, and it is clear that detergents can have detrimental effects on GPCR function. Simultaneously, there is increasing appreciation of roles for specific lipids in modulation of GPCR function. Lipid nanoparticles such as nanodiscs and styrene maleic acid lipid particles (SMALPs) offer opportunities to study integral membrane proteins in lipid environments, in a form that is soluble and amenable to structural and biophysical experiments. Here, we review the application of lipid nanoparticle technologies to the study of GPCRs, assessing the relative merits and limitations of each system. We highlight how these technologies can provide superior platforms to detergents for structural and biophysical studies of GPCRs and inform on roles for protein-lipid interactions in GPCR function.
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- 2020
13. An integrated geophysical approach for imaging of the Semail ophiolite
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Simone Pilia, Mohammed Ali, Mike Searle, Anthony Watts, Brook Keats, and Tyler Ambrose
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The Semail ophiolite, a thick thrust sheet of Late Cretaceous oceanic crust and upper mantle, was obducted onto the previously rifted Arabian continental margin in the Late Cretaceous, and now forms part of the United Arab Emirates (UAE)-Oman mountain belt. A deep foreland basin along the west and SW margin of the mountains developed during the obduction process, as a result of flexure due to loading of the ophiolite and underlying thrust sheets. Structural and compositional complexities (e.g., presence of thick sand dunes, relatively shallow high-velocity and dense ophiolite structure) have made geophysical imaging of the sub-ophiolite and mid-lower crustal structure particularly challenging.A combination of active and passive-source seismic techniques, potential field modelling and surface geological mapping are used to constrain the stratigraphy, velocity structure and crustal thickness beneath the UAE-Oman mountains and its bounding basins. Depth-migrated multichannel seismic-reflection profile data are integrated in the modeling of traveltimes from long offset reflections and refractions, which are used to resolve the crustal thickness and velocity structure along two E-W onshore/offshore transects in the UAE. Additionally, we apply receiver function and virtual deep seismic sounding methods to distant earthquake data recorded along the two transects to image crustal thickness variations. Seismic and geological constraints from the transects have been finally used to model gravity and magnetic anomaly data along two coincident profiles.Geophysical methods define the Semail ophiolite as a high-velocity, high density, > 15 km thick body dipping to the east. The western limit of the ophiolite is defined onshore by the Semail thrust while the eastern limit extends several km offshore, where it is defined seismically by a ~40–45° normal fault. Emplacement of the ophiolite has probably flexed down a previously rifted continental margin, thus contributing to subsidence of flanking sedimentary basins. The new crustal thickness model presented in this work provides evidence that a crustal root is present beneath the Semail ophiolite, suggesting that folding and thrusting during the obduction process may have thickened the pre-existing crust by 16 km.
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- 2022
14. Geophysical imaging of ophiolite structure in the United Arab Emirates
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Brook Keats, Simone Pilia, Mohammed Y. Ali, Michael P. Searle, Anthony Watts, Tyler K. Ambrose, Ali, MY [0000-0001-7502-3897], Watts, AB [0000-0002-2198-2942], Apollo - University of Cambridge Repository, Ali, M, Watts, A, Searle, M, Keats, B, Pilia, S, and Ambrose, T
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010504 meteorology & atmospheric sciences ,Science ,General Physics and Astronomy ,3705 Geology ,sub-02 ,010502 geochemistry & geophysics ,Ophiolite ,01 natural sciences ,General Biochemistry, Genetics and Molecular Biology ,Article ,semail ophiolite ,Paleontology ,Continental margin ,Oceanic crust ,Semail Ophiolite ,Thrust fault ,lcsh:Science ,0105 earth and related environmental sciences ,geography ,Multidisciplinary ,geography.geographical_feature_category ,Structural geology ,Tectonics ,Eurasian Plate ,Crust ,37 Earth Sciences ,General Chemistry ,Sedimentary basin ,Geophysics ,lcsh:Q ,3706 Geophysics ,Geology - Abstract
The Oman-United Arab Emirates ophiolite has been used extensively to document the geological processes that form oceanic crust. The geometry of the ophiolite, its extension into the Gulf of Oman, and the nature of the crust that underlies it are, however, unknown. Here, we show the ophiolite forms a high velocity, high density, >15 km thick east-dipping body that during emplacement flexed down a previously rifted continental margin thereby contributing to subsidence of flanking sedimentary basins. The western limit of the ophiolite is defined onshore by the Semail thrust while the eastern limit extends several km offshore, where it is defined seismically by a ~40–45°, east-dipping, normal fault. The fault is interpreted as the southwestern margin of an incipient suture zone that separates the Arabian plate from in situ Gulf of Oman oceanic crust and mantle presently subducting northwards beneath the Eurasian plate along the Makran trench., The Semail ophiolite provides evidence for geological processes that form oceanic crust, however, its deep structure remains debated. Here, the authors use geophysical imaging to determine that the ophiolite is bound by a thrust fault in the west, and a normal fault in the east, bounding a rapidly subsiding basin, implying the ophiolite may not be rooted in the Gulf of Oman crust.
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- 2020
15. Conformational flexibility of GRASPs and their constituent PDZ subdomains reveals structural basis of their promiscuous interactome
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Antonio J. Costa-Filho, Luis Felipe S. Mendes, Christina Redfield, Mariana R. B. Batista, Peter J. Judge, and Anthony Watts
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0301 basic medicine ,Protein Conformation ,PDZ domain ,Stacking ,PDZ Domains ,Sequence Homology ,Molecular Dynamics Simulation ,Crystallography, X-Ray ,Biochemistry ,Interactome ,03 medical and health sciences ,symbols.namesake ,Molecular dynamics ,0302 clinical medicine ,Humans ,Amino Acid Sequence ,Molecular Biology ,Protein secondary structure ,Secretory pathway ,Chemistry ,Golgi Matrix Proteins ,Cell Biology ,Golgi apparatus ,030104 developmental biology ,030220 oncology & carcinogenesis ,Helix ,symbols ,Biophysics ,Protein Binding - Abstract
The Golgi complex is a central component of the secretory pathway, responsible for several critical cellular functions in eukaryotes. The complex is organized by the Golgi matrix that includes the Golgi reassembly and stacking protein (GRASP), which was shown to be involved in cisternae stacking and lateral linkage in metazoan. GRASPs also have critical roles in other processes, with an unusual ability to interact with several different binding partners. The conserved N terminus of the GRASP family includes two PSD-95, DLG, and ZO-1 (PDZ) domains. Previous crystallographic studies of orthologues suggest that PDZ1 and PDZ2 have similar conformations and secondary structure content. However, PDZ1 alone mediates nearly all interactions between GRASPs and their partners. In this work, NMR, synchrotron radiation CD, and molecular dynamics (MD) were used to examine the structure, flexibility, and stability of the two constituent PDZ domains. GRASP PDZs are structured in an unusual β3 α1 β4 β5 α2 β6 β1 β2 secondary structural arrangement and NMR data indicate that the PDZ1 binding pocket is formed by a stable β2 -strand and a more flexible and unstable α2 -helix, suggesting an explanation for the higher PDZ1 promiscuity. The conformational free energy profiles of the two PDZ domains were calculated using MD simulations. The data suggest that, after binding, the protein partner significantly reduces the conformational space that GRASPs can access by stabilizing one particular conformation, in a partner-dependent fashion. The structural flexibility of PDZ1, modulated by PDZ2, and the coupled, coordinated movement between the two PDZs enable GRASPs to interact with multiple partners, allowing them to function as promiscuous, multitasking proteins.
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- 2020
16. In vivo observation of amyloid-like fibrils produced under stress
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Natália A. Fontana, Ariane D. Rosse, Anthony Watts, Paulo S.R. Coelho, and Antonio J. Costa-Filho
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Amyloid ,Saccharomyces cerevisiae Proteins ,Structural Biology ,Escherichia coli ,Protein Conformation, beta-Strand ,ORGANELAS CELULARES ,General Medicine ,Saccharomyces cerevisiae ,Molecular Biology ,Biochemistry - Abstract
The participation of amyloids in neurodegenerative diseases and functional processes has triggered the quest for methods allowing their direct detection in vivo. Despite the plethora of data, those methods are still lacking. The autofluorescence from the extended β-sheets of amyloids is here used to track fibrillation of S. cerevisiae Golgi Reassembly and Stacking Protein (Grh1). Grh1 has been implicated in starvation-triggered unconventional protein secretion (UPS), and here its participation also in heat shock response (HSR) is suggested. Fluorescence Lifetime Imaging (FLIM) is used to detect fibril autofluorescence in cells (E. coli and yeast) under stress (starvation and higher temperature). The formation of Grh1 large complexes under stress is further supported by size exclusion chromatography and ultracentrifugation. The data show for the first time in vivo detection of amyloids without the use of extrinsic probes as well as bring new perspectives on the participation of Grh1 in UPS and HSR.
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- 2022
17. Structures of the archaerhodopsin-3 transporter reveal that disordering of internal water networks underpins receptor sensitization
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Carol V. Robinson, Hsin-Yung Yen, Juan F. Bada Juarez, Kin Kuan Hoi, Igor Schapiro, Danny Axford, Anthony Vial, Anthony Watts, Isabel Moraes, Suliman Adam, James M. Birch, J. Vinals, Tristan O. C. Kwan, Pierre-Emmanuel Milhiet, Peter J. Judge, Department of Biochemistry [Oxford], University of Oxford [Oxford], The Fritz Haber Research Center for Molecular Dynamics [Jerusalem], The Hebrew University of Jerusalem (HUJ), DIAMOND Light source, Diamond Light Source Limited [Didcot, UK], Harwell Science and Innovation Campus [Didcot, UK], Rutherford Appleton Laboratory, Research Complex at Harwell, Chemistry Research Laboratory [Oxford, UK], Omas therapeutics, Centre de Biochimie Structurale [Montpellier] (CBS), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Oxford, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and Milhiet, Pierre-Emmanuel
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0301 basic medicine ,[SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM] ,Science ,Archaeal Proteins ,Molecular Conformation ,General Physics and Astronomy ,Electrons ,Optogenetics ,Crystallography, X-Ray ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,Computational biophysics ,Membrane biophysics ,0302 clinical medicine ,Isomerism ,Membrane proteins ,Receptor ,X-ray crystallography ,Membrane potential ,Multidisciplinary ,[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM] ,Membrane Transport Proteins ,Water ,Retinal ,Hydrogen Bonding ,General Chemistry ,Chromophore ,Lipids ,030104 developmental biology ,chemistry ,Biophysics ,Retinaldehyde ,Bacterial rhodopsins ,sense organs ,Protons ,Ground state ,Isomerization ,Protein Processing, Post-Translational ,030217 neurology & neurosurgery - Abstract
Many transmembrane receptors have a desensitized state, in which they are unable to respond to external stimuli. The family of microbial rhodopsin proteins includes one such group of receptors, whose inactive or dark-adapted (DA) state is established in the prolonged absence of light. Here, we present high-resolution crystal structures of the ground (light-adapted) and DA states of Archaerhodopsin-3 (AR3), solved to 1.1 Å and 1.3 Å resolution respectively. We observe significant differences between the two states in the dynamics of water molecules that are coupled via H-bonds to the retinal Schiff Base. Supporting QM/MM calculations reveal how the DA state permits a thermodynamic equilibrium between retinal isomers to be established, and how this same change is prevented in the ground state in the absence of light. We suggest that the different arrangement of internal water networks in AR3 is responsible for the faster photocycle kinetics compared to homologs., Archaerhodopsin-3 (AR3) mutants are commonly used in optogenetics for neuron silencing and membrane voltage sensing. High-resolution crystal structures show that desensitization of the AR3 photoreceptor occurs when internal hydrogen-bonded water networks are modified in response to changes in chromophore isomerization.
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- 2021
18. Crustal and Mantle Deformation Inherited From Obduction of the Semail Ophiolite (Oman) and Continental Collision (Zagros)
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Simone Pilia, Michael P. Searle, Ayoub Kaviani, Anthony Watts, Mohammed Y. Ali, P. Arroucau, Pilia, S [0000-0002-3805-9257], Kaviani, A [0000-0001-5818-1594], Searle, MP [0000-0001-6904-6398], Watts, AB [0000-0002-2198-2942], Apollo - University of Cambridge Repository, Pilia, S, Kaviani, A, Searle, M, Arroucau, P, Ali, M, and Watts, A
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syntaxi ,010504 meteorology & atmospheric sciences ,Subduction ,Continental collision ,Geochemistry ,Zagros mountain ,anisotropy ,010502 geochemistry & geophysics ,Ophiolite ,01 natural sciences ,Mantle (geology) ,Zagros mountains ,Obduction ,semail ophiolite ,Geophysics ,Geochemistry and Petrology ,Lithosphere ,Semail Ophiolite ,Tectonophysics ,syntaxis ,lithosphere ,shear-wave splitting ,Geology ,0105 earth and related environmental sciences - Abstract
A common deviation from typical subduction models occurs when thrust sheets of oceanic crust and upper‐mantle rocks are emplaced over more buoyant continental lithosphere. The archetypal example of ophiolite obduction is the Semail ophiolite in the United Arab Emirates (UAE)‐Oman orogenic belt, formed and obducted onto the Arabian continental margin during the Late Cretaceous. The Strait of Hormuz syntaxis, the northern extent of the UAE‐Oman mountains, marks the transition from ocean‐continent convergence in the Gulf of Oman to continental collision along the Zagros Mountains. Based on new seismic data from a focused recording network, we infer continental crustal and mantle deformation in the northeastern corner of the Arabian plate (including the southern Zagros and the UAE‐Oman mountains), using observations from anisotropic tomography and shear‐wave splitting (SWS) measurements. We recover a change of ∼90° (from approximately WNW to nearly NS) in the axis of fast‐anisotropic orientations in the crust from the Zagros to the UAE‐Oman mountain belt, consistent with the dominant strike of the orogenic belts. We also find evidence in our SWS parameters for localized fossil deformation in the lithospheric mantle underlying the UAE‐Oman mountain range, possibly related to stress‐induced tectonism triggered by north‐east oriented underthrusting of the proto‐Arabian continental margin beneath the overriding Semail ophiolite. Shear‐wave‐splitting anisotropy orientations along two transects across the northern Musandam peninsula, averaging 15° anticlockwise from the north, provide the first geophysical verification of previous geological evidence that suggests a NE polarity of the Late Cretaceous Oman subduction zone system.
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- 2021
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19. Detergent-free Lipodisq Nanoparticles Facilitate High-Resolution Mass Spectrometry of Folded Integral Membrane Proteins
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Carol V. Robinson, Di Wu, J. Vinals, Hsin-Yung Yen, Kin Kuan Hoi, Juan F. Bada Juarez, Anthony Watts, Garrick F. Taylor, and Peter J. Judge
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Scaffold protein ,Letter ,Lipid Bilayers ,Bioengineering ,02 engineering and technology ,Mass spectrometry ,Micelle ,Mass Spectrometry ,Native mass spectrometry ,General Materials Science ,Integral membrane protein ,Micelles ,SMALP ,biology ,Chemistry ,lipid−protein interactions ,bacteriorhodopsin ,Mechanical Engineering ,Photoreceptor protein ,Membrane Proteins ,Bacteriorhodopsin ,General Chemistry ,Lipodisq ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,Lipids ,Membrane ,Membrane protein ,post-translational modification ,Biophysics ,biology.protein ,Nanoparticles ,0210 nano-technology - Abstract
Integral membrane proteins pose considerable challenges to mass spectrometry (MS) owing to the complexity and diversity of the components in their native environment. Here, we use native MS to study the post-translational maturation of bacteriorhodopsin (bR) and archaerhodopsin-3 (AR3), using both octyl-glucoside detergent micelles and lipid-based nanoparticles. A lower collision energy was required to obtain well-resolved spectra for proteins in styrene-maleic acid copolymer (SMA) Lipodisqs than in membrane scaffold protein (MSP) Nanodiscs. By comparing spectra of membrane proteins prepared using the different membrane mimetics, we found that SMA may favor selective solubilization of correctly folded proteins and better preserve native lipid interactions than other membrane mimetics. Our spectra reveal the correlation between the post-translation modifications (PTMs), lipid-interactions, and protein-folding states of bR, providing insights into the process of maturation of the photoreceptor proteins.
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- 2021
20. Seismic Structure, Gravity Anomalies and Flexure Along the Emperor Seamount Chain
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Anthony Watts, B. Boston, Robert Dunn, D. J. Shillington, Ingo Grevemeyer, and L. Gómez de la Peña
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geography ,geography.geographical_feature_category ,010504 meteorology & atmospheric sciences ,biology ,Seamount ,010502 geochemistry & geophysics ,biology.organism_classification ,01 natural sciences ,Gravity anomaly ,Geophysics ,Chain (algebraic topology) ,Space and Planetary Science ,Geochemistry and Petrology ,Earth and Planetary Sciences (miscellaneous) ,Emperor ,14. Life underwater ,Geology ,Seismology ,0105 earth and related environmental sciences - Abstract
The Hawaiian-Emperor seamount chain in the Pacific Ocean has provided fundamental insights into hotspot generated intraplate volcanism and the long-term strength of oceanic lithosphere. However, only a few seismic experiments to determine crustal and upper mantle structure have been carried out on the Hawaiian Ridge, and no deep imaging has ever been carried out along the Emperor seamounts. Here, we present the results of an active source seismic experiment using 29 Ocean-Bottom Seismometers (OBS) carried out along a strike profile of the seamounts in the region of Jimmu and Suiko guyots. Joint reflection and refraction tomographic inversion of the OBS data show the upper crust is highly heterogeneous with P wave velocities
- Published
- 2021
21. In vivo amyloid-like fibrils produced under stress
- Author
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P. S. R. Coelho, Anthony Watts, Antonio J. Costa-Filho, Natália A. Fontana, and Ariane D. Rosse
- Subjects
Unconventional protein secretion ,Autofluorescence ,Fluorescence-lifetime imaging microscopy ,Chemistry ,In vivo ,Biophysics ,Golgi reassembly ,Ultracentrifuge ,Heat shock ,Fibril - Abstract
The participation of amyloids in neurodegenerative diseases and functional processes has triggered the quest for methods allowing their direct detection in vivo. Despite the plethora of data, those methods are still lacking. The autofluorescence from the extended β-sheets of amyloids is here used to follow fibrillation of S. cerevisiae Golgi Reassembly and Stacking Protein (Grh1). Grh1 has been implicated in starvation-triggered unconventional protein secretion (UPS), and here its participation also in heat shock response (HSR) is suggested. Fluorescence Lifetime Imaging (FLIM) is used to detect fibril autofluorescence in cells (E. coli and yeast) under stress (starvation and higher temperature). The formation of Grh1 large complexes under stress is further supported by size exclusion chromatography and ultracentrifugation. The data show for the first time in vivo detection of amyloids without the use of extrinsic probes as well as bring new perspectives on the participation of Grh1 in UPS and HSR.
- Published
- 2021
22. Crustal structure of the UAE-Oman mountain range and Arabian rifted passive margin: new constraints from active and passive seismic methods
- Author
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Anthony Watts, Simone Pilia, Mohammed Y. Ali, David Thompson, ChuanChuan Lü, Michael P. Searle, Pilia, S, Ali, M, Searle, M, Watts, A, Lu, C, and Thompson, D
- Subjects
010504 meteorology & atmospheric sciences ,flexure ,crustal thickne ,01 natural sciences ,Obduction ,Nappe ,semail ophiolite ,Paleontology ,Continental margin ,sedimentary basin ,Geochemistry and Petrology ,Passive margin ,Oceanic crust ,Semail Ophiolite ,Earth and Planetary Sciences (miscellaneous) ,14. Life underwater ,0105 earth and related environmental sciences ,geography ,geography.geographical_feature_category ,Sedimentary basin ,Cretaceous ,Geophysics ,Space and Planetary Science ,obduction ,virtual deep seismic sounding ,Geology - Abstract
The Semail ophiolite, a thick thrust sheet of Late Cretaceous oceanic crust and upper mantle, was obducted onto the previously rifted Arabian continental margin in the Late Cretaceous, and now forms part of the United Arab Emirates (UAE)-Oman mountain belt. A deep foreland basin along the west and SW margin of the mountains developed during the obduction process, as a result of flexure due to loading of the ophiolite and underlying thrust sheets. The nature of the crust beneath the deep sedimentary basins that flank the mountain belt, and the extent to which the Arabian continental crust has thickened due to the obduction process are outstanding questions. We use a combination of active- and passive-source seismic data to constrain the stratigraphy, velocity structure and crustal thickness beneath the UAE-Oman mountains and its bounding basins. Depth-migrated multichannel seismic reflection profile data are integrated in the modeling of traveltimes from long offset reflections and refractions, which are used to resolve the crustal thickness and velocity structure along two E-W onshore/offshore transects in the UAE. Additionally, we apply the virtual deep seismic sounding method to distant earthquake data recorded along the two transects to image crustal thickness variations. Active seismic methods define the Semail ophiolite as a high-velocity body dipping to the east at 40°–45°. The new crustal thickness model presented in this work provides evidence that a crustal root is present beneath the Semail ophiolite, suggesting that folding and thrusting during the obduction process may have thickened the pre-existing crust by 16km.
- Published
- 2021
23. Structures of the archaerhodopsin-3 transporter reveal that disordering of internal water networks underpins receptor sensitization
- Author
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Peter J. Judge, Juan Francisco Bada Juarez, Danny Axford, Isabel Moraes, and Anthony Watts
- Subjects
Biophysics - Published
- 2022
24. Evaluation of Shipboard and Satellite‐Derived Bathymetry and Gravity Data Over Seamounts in the Northwest Pacific Ocean
- Author
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Robert Dunn, B. Tozer, Hugh Harper, Anthony Watts, D. J. Shillington, and B. Boston
- Subjects
Gravity (chemistry) ,geography ,Geophysics ,Oceanography ,geography.geographical_feature_category ,Space and Planetary Science ,Geochemistry and Petrology ,Seamount ,Earth and Planetary Sciences (miscellaneous) ,Satellite ,Bathymetry ,Pacific ocean ,Geology - Published
- 2020
25. Physicochemical characterization, toxicity and in vivo biodistribution studies of a discoidal, lipid-based drug delivery vehicle: Lipodisq nanoparticles containing doxorubicin
- Author
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Tore Skotland, Gunhild Mari Mælandsmo, Matylda K. Maciejewska, Markus Fusser, Daniel J. Yin, Abhilash D. Pandya, Peter J. Judge, Maria Lyngaas Torgersen, Kirsten Sandvig, Charlie W. Davies, Juan F. Bada Juarez, and Anthony Watts
- Subjects
Biodistribution ,biology ,Chemistry ,0206 medical engineering ,Biomedical Engineering ,Pharmaceutical Science ,Medicine (miscellaneous) ,Bioengineering ,02 engineering and technology ,021001 nanoscience & nanotechnology ,biology.organism_classification ,020601 biomedical engineering ,Bioavailability ,HeLa ,In vivo ,Drug delivery ,Biophysics ,General Materials Science ,0210 nano-technology ,Cytotoxicity ,Lipid bilayer ,Intracellular - Abstract
Many promising pharmaceutically active compounds have low solubility in aqueous environments and their encapsulation into efficient drug delivery vehicles is crucial to increase their bioavailability. Lipodisq nanoparticles are approximately 10 nm in diameter and consist of a circular phospholipid bilayer, stabilized by an annulus of SMA (a hydrolysed copolymer of styrene and maleic anhydride). SMA is used extensively in structural biology to extract and stabilize integral membrane proteins for biophysical studies. Here, we assess the potential of these nanoparticles as drug delivery vehicles, determining their cytotoxicity and the in vivo excretion pathways of their polymer and lipid components. Doxorubicin-loaded Lipodisqs were cytotoxic across a panel of cancer cell lines, whereas nanoparticles without the drug had no effect on cell proliferation. Intracellular doxorubicin release from Lipodisqs in HeLa cells occurred in the low-pH environment of the endolysosomal system, consistent with the breakdown of the discoidal structure as the carboxylate groups of the SMA polymer become protonated. Biodistribution studies in mice showed that, unlike other nanoparticles injected intravenously, most of the Lipodisq components were recovered in the colon, consistent with rapid uptake by hepatocytes and excretion into bile. These data suggest that Lipodisqs have the potential to act as delivery vehicles for drugs and contrast agents.
- Published
- 2020
26. Constitutive activity of the dual-chromophore photoreceptor Archaerhodopsin 4
- Author
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Xiaoyan Ding, Haolin Cui, Anthony Watts, Qixi Mi, Xin Zhao, Chao Sun, Dongxue Liu, Xiao He, and Sijin Chen
- Subjects
Chemistry ,Biophysics ,Bacterial rhodopsins ,Chromophore ,DUAL (cognitive architecture) - Published
- 2020
27. From polymer chemistry to structural biology: The development of SMA and related amphipathic polymers for membrane protein extraction and solubilisation
- Author
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Anthony Watts, Peter J. Judge, Andrew Harper, Stephen Tonge, and Juan F. Bada Juarez
- Subjects
Molecular Structure ,Polymers ,Chemistry ,Organic Chemistry ,Membrane Proteins ,Cell Biology ,Biochemistry ,Transmembrane protein ,Surface-Active Agents ,Protein structure ,Solubility ,Membrane protein ,Structural biology ,Amphiphile ,Native state ,Biophysics ,Molecular Biology ,Styrene ,Alpha helix ,Nanodisc ,Maleic Anhydrides - Abstract
Nanoparticles assembled with poly(styrene-maleic acid) copolymers, identified in the literature as Lipodisq, SMALPs or Native Nanodisc, are routinely used as membrane mimetics to stabilise protein structures in their native conformation. To date, transmembrane proteins of varying complexity (up to 8 beta strands or 48 alpha helices) and of a range of molecular weights (from 27 kDa up to 500 kDa) have been incorporated into this particle system for structural and functional studies. SMA and related amphipathic polymers have become versatile components of the biochemist's tool kit for the stabilisation, extraction and structural characterization of membrane proteins by techniques including cryo-EM and X-ray crystallography. Lipodisq formation does not require the use of conventional detergents and thus avoids their associated detrimental consequences. Here the development of this technology, from its fundamental concept and design to the diverse range of experimental methodologies to which it can now be applied, will be reviewed.
- Published
- 2020
28. Tuneable poration: host defense peptides as sequence probes for antimicrobial mechanisms
- Author
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Jason Crain, Valeria Losasso, Martyn Winn, Hasan Alkassem, Peter J. Judge, Maxim G. Ryadnov, Nilofar Faruqui, Bart W. Hoogenboom, Marc-Philipp Pfeil, Anthony Watts, Katharine Hammond, Baptiste Lamarre, Glenn J. Martyna, Jascindra Ravi, and Alice L. B. Pyne
- Subjects
0301 basic medicine ,Multidisciplinary ,030102 biochemistry & molecular biology ,Drug discovery ,Chemistry ,lcsh:R ,Cecropin B ,lcsh:Medicine ,Sequence (biology) ,Computational biology ,Drug resistance ,Antimicrobial ,Article ,03 medical and health sciences ,030104 developmental biology ,lcsh:Q ,lcsh:Science ,Peptide sequence - Abstract
The spread of antimicrobial resistance stimulates discovery strategies that place emphasis on mechanisms circumventing the drawbacks of traditional antibiotics and on agents that hit multiple targets. Host defense peptides (HDPs) are promising candidates in this regard. Here we demonstrate that a given HDP sequence intrinsically encodes for tuneable mechanisms of membrane disruption. Using an archetypal HDP (cecropin B) we show that subtle structural alterations convert antimicrobial mechanisms from native carpet-like scenarios to poration and non-porating membrane exfoliation. Such distinct mechanisms, studied using low- and high-resolution spectroscopy, nanoscale imaging and molecular dynamics simulations, all maintain strong antimicrobial effects, albeit with diminished activity against pathogens resistant to HDPs. The strategy offers an effective search paradigm for the sequence probing of discrete antimicrobial mechanisms within a single HDP.
- Published
- 2020
29. Physicochemical characterization, toxicity andin vivobiodistribution studies of a discoidal, lipid-based drug delivery vehicle: Lipodisq nanoparticles containing doxorubicin
- Author
-
Juan F. Bada Juarez, Markus Fusser, Gunhild Mari Mælandsmo, Maria Lyngaas Torgersen, Abhilash D. Pandya, Matylda K. Maciejewska, Anthony Watts, Kirsten Sandvig, Daniel J. Yin, Charlie W. Davies, Tore Skotland, and Peter J. Judge
- Subjects
HeLa ,Biodistribution ,biology ,In vivo ,Chemistry ,Drug delivery ,Biophysics ,Lipid bilayer ,biology.organism_classification ,Cytotoxicity ,Intracellular ,Bioavailability - Abstract
Many promising pharmaceutically active compounds have low solubility in aqueous environments and their encapsulation into efficient drug delivery vehicles is crucial to increase their bioavailability. Lipodisq nanoparticles are approximately 10 nm in diameter and consist of a circular phospholipid bilayer, stabilized by an annulus of SMA (a hydrolysed copolymer of styrene and maleic anhydride). SMA is used extensively in structural biology to extract and stabilize integral membrane proteins for biophysical studies. Here, we assess the potential of these nanoparticles as drug delivery vehicles, determining their cytotoxicity and thein vivoexcretion pathways of their polymer and lipid components. Doxorubicin-loaded Lipodisqs were cytotoxic across a panel of cancer cell lines, whereas nanoparticles without the drug had no effect on cell proliferation. Intracellular doxorubicin release from Lipodisqs in HeLa cells occurred in the low-pH environment of the endolysosomal system, consistent with the breakdown of the discoidal structure as the carboxylate groups of the SMA polymer become protonated. Biodistribution studies in mice showed that, unlike other nanoparticles injected intravenously, most of the Lipodisq components were recovered in the colon, consistent with rapid uptake by hepatocytes and excretion into bile. These data suggest that Lipodisqs have the potential to act as delivery vehicles for drugs and contrast agents.
- Published
- 2020
30. Tectonics and Landscape of the Central African Plateau and their Implications for a Propagating Southwestern Rift in Africa
- Author
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O. Davies, P. Green, Richard Walker, M. C. Daly, F. Chibesakunda, and Anthony Watts
- Subjects
Tectonics ,Paleontology ,geography ,Geophysics ,Rift ,Plateau ,geography.geographical_feature_category ,Geochemistry and Petrology ,Geology - Published
- 2020
31. Detergent-free solubilisationpurification of a G protein coupled receptor using a polymethacrylate polymer
- Author
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Anthony Watts and Steven Lavington
- Subjects
0303 health sciences ,Chemistry ,Detergents ,Biophysics ,Cell Biology ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Fusion protein ,Recombinant Proteins ,0104 chemical sciences ,03 medical and health sciences ,Membrane ,Membrane protein ,Polymethacrylic Acids ,Solubility ,Heterotrimeric G protein ,Amphiphile ,Humans ,Receptors, Neurotensin ,Lipid bilayer ,Receptor ,030304 developmental biology ,G protein-coupled receptor - Abstract
G protein coupled receptors (GPCRs) function as guanine nucleotide exchange factors (GEFs) at heterotrimeric G proteins, and conduct this role embedded in a lipid bilayer. Detergents are widely used to solubilise GPCRs for structural and biophysical analysis, but are poor mimics of the lipid bilayer and may be deleterious to protein function. Amphipathic polymers have emerged as promising alternatives to detergents, which maintain a lipid environment around a membrane protein during purification. Of these polymers, the polymethacrylate (PMA) polymers have potential advantages over the most popular styrene maleic acid (SMA) polymer, but to date have not been applied to purification of membrane proteins. Here we use a class A GPCR, neurotensin receptor 1 (NTSR1), to explore detergent-free purification using PMA. By using an NTSR1-eGFP fusion protein expressed in Sf9 cells, a range of solubilisation conditions were screened, demonstrating the importance of solubilisation temperature, pH, NaCl concentration and the relative amounts of polymer and membrane sample. PMA-solubilised NTSR1 displayed compatibility with standard purification protocols and millimolar divalent cation concentrations. Moreover, the receptor in PMA discs showed stimulation of both Gq and Gi1 heterotrimers to an extent that was greater than that for the detergent-solubilised receptor. PMA therefore represents a viable alternative to SMA for membrane protein purification and has a potentially broad utility in studying GPCRs and other membrane proteins.
- Published
- 2020
32. Membrane Proteins: Structure and Organization
- Author
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John A. Linney, Joanne Oates, Annaïg J. Rozo, Anthony Watts, Alan D. Goddard, Roberts, Gordon, and Watts, Anthony
- Subjects
0303 health sciences ,03 medical and health sciences ,Membrane protein ,Chemistry ,030302 biochemistry & molecular biology ,Biophysics ,030304 developmental biology - Published
- 2020
33. Membrane Protein Function
- Author
-
Alan Goddard, María M. Román Lara, Peer Depping, Joanne Oates, Anthony Watts, Roberts, Gordon, and Watts, Anthony
- Subjects
0303 health sciences ,03 medical and health sciences ,0302 clinical medicine ,Membrane protein ,Chemistry ,Biophysics ,030212 general & internal medicine ,Function (biology) ,030304 developmental biology ,Cell biology - Published
- 2020
- Full Text
- View/download PDF
34. Conformational dynamics of a G protein-coupled receptor helix 8 in lipid membranes
- Author
-
Antonio J. Costa-Filho, Patricia M. Dijkman, Juan C. Muñoz-García, Anthony Watts, Rosana I. Reis, Steven Lavington, Daniel Yin, Phillip J. Stansfeld, and Patricia S. Kumagai
- Subjects
RM ,Circular dichroism ,Neurotensin receptor 1 ,POLÍMEROS (MATERIAIS) ,Molecular Conformation ,Biophysics ,Molecular Dynamics Simulation ,digestive system ,complex mixtures ,Receptors, G-Protein-Coupled ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Structural Biology ,Humans ,Receptor ,QH426 ,Research Articles ,030304 developmental biology ,G protein-coupled receptor ,Phosphatidylethanolamine ,0303 health sciences ,Arrestin ,Multidisciplinary ,musculoskeletal, neural, and ocular physiology ,digestive, oral, and skin physiology ,SciAdv r-articles ,Lipids ,Membrane protein ,chemistry ,Helix ,hormones, hormone substitutes, and hormone antagonists ,030217 neurology & neurosurgery ,Alpha helix ,Research Article - Abstract
Helix 8 of the GPCR neurotensin receptor 1 is stabilised by specific lipid-protein interactions., G protein–coupled receptors (GPCRs) are the largest and pharmaceutically most important class of membrane proteins encoded in the human genome, characterized by a seven-transmembrane helix architecture and a C-terminal amphipathic helix 8 (H8). In a minority of GPCR structures solved to date, H8 either is absent or adopts an unusual conformation. The controversial existence of H8 of the class A GPCR neurotensin receptor 1 (NTS1) has been examined here for the nonthermostabilized receptor in a functionally supporting membrane environment using electron paramagnetic resonance, molecular dynamics simulations, and circular dichroism. Lipid-protein interactions with phosphatidylserine and phosphatidylethanolamine lipids, in particular, stabilize the residues 374 to 390 of NTS1 into forming a helix. Furthermore, introduction of a helix-breaking proline residue in H8 elicited an increase in ß-arrestin–NTS1 interactions observed in pull-down assays, suggesting that the structure and/or dynamics of H8 might play an important role in GPCR signaling.
- Published
- 2020
35. Updated seafloor topography and T phase seismicity at Monowai, northern Kermadec Arc
- Author
-
Anthony Watts, Reinhard Werner, Dirk Metz, Ingo Grevemeyer, and Hannes Huusmann
- Subjects
geography ,geography.geographical_feature_category ,010504 meteorology & atmospheric sciences ,Submarine ,Geology ,Induced seismicity ,010502 geochemistry & geophysics ,01 natural sciences ,Pacific ocean ,Seafloor spreading ,Arc (geometry) ,Submarine eruption ,Geophysics ,Volcano ,Earth and Planetary Sciences (miscellaneous) ,14. Life underwater ,Submarine volcano ,Seismology ,0105 earth and related environmental sciences - Abstract
Monowai is an active submarine volcanic centre in the Kermadec Arc, Southwest Pacific Ocean. Multi-beam data acquired during expedition SO225 aboard R/V SONNE in December 2012 indicates that the topography of the main stratocone has evolved significantly since the last survey in June 2011. Bathymetric measurements of the edifice reveal differences of up to 42 m in seafloor depth and indicate a net volume increase of ∼0.037 km3 across the summit area. Explosive volcanism observed onsite during the SO225 mapping campaign could be linked to a 20h-long swarm of unusually coherent T phase arrivals, suggesting that Monowai is a prime source of broadband seismic noise in the Southwest Pacific region during times of activity. Our findings further document the dynamic nature of volcanic processes at Monowai and have implications for future expedition planning.
- Published
- 2020
- Full Text
- View/download PDF
36. Functional roles of tyrosine 185 during the bacteriorhodopsin photocycle as revealed by in situ spectroscopic studies
- Author
-
Yanan Yang, Xiao He, Haolin Cui, Chao Sun, Sijin Chen, Xiaoyan Ding, Juan Wang, Xin Zhao, Anthony Watts, Fang Tian, Dinu Iuga, and Yujiao Gao
- Subjects
0301 basic medicine ,030102 biochemistry & molecular biology ,biology ,Chemistry ,Protein dynamics ,Mutagenesis ,Biophysics ,Bacteriorhodopsin ,Cell Biology ,Chromophore ,Biochemistry ,03 medical and health sciences ,030104 developmental biology ,Dynamic light scattering ,Helix ,biology.protein ,Tyrosine ,Conformational isomerism - Abstract
Tyrosine 185 (Y185), one of the aromatic residues within the retinal (Ret) chromophore binding pocket in helix F of bacteriorhodopsin (bR), is highly conserved among the microbial rhodopsin family proteins. Many studies have investigated the functions of Y185, but its underlying mechanism during the bR photocycle remains unclear. To address this research gap, in situ two-dimensional (2D) magic-angle spinning (MAS) solid-state NMR (ssNMR) of specifically labelled bR, combined with light-induced transient absorption change measurements, dynamic light scattering (DLS) measurements, titration analysis and site-directed mutagenesis, was used to elucidate the functional roles of Y185 during the bR photocycle in the native membrane environment. Different interaction modes were identified between Y185 and the Ret chromophore in the dark-adapted (inactive) state and M (active) state, indicating that Y185 may serve as a rotamer switch maintaining the protein dynamics, and plays an important role in the efficient proton-pumping mechanism in the bR purple membrane.
- Published
- 2018
37. Tracking Submarine Volcanic Activity at Monowai: Constraints From Long-Range Hydroacoustic Measurements
- Author
-
Ingo Grevemeyer, D. Metz, Anthony Watts, and Mel Rodgers
- Subjects
geography ,geography.geographical_feature_category ,010504 meteorology & atmospheric sciences ,Hydrophone ,Submarine ,Volcanism ,Induced seismicity ,010502 geochemistry & geophysics ,01 natural sciences ,Seafloor spreading ,Geophysics ,Volcano ,13. Climate action ,Space and Planetary Science ,Geochemistry and Petrology ,Hydroacoustics ,Earth and Planetary Sciences (miscellaneous) ,14. Life underwater ,Underwater ,Geology ,Seismology ,0105 earth and related environmental sciences - Abstract
Monowai is a submarine volcanic center in the Kermadec Arc, Southwest Pacific Ocean. In the past, activity at the volcano had been intermittently observed in the form of fallout at the sea surface, discolored water, changes in seafloor topography, and T phase seismicity, but there is no continuous record for more recent years. In this study, we investigated 3.5 years of recordings at a hydrophone array of the International Monitoring System (IMS), located near Juan Fernandez Islands for long‐range underwater sound waves from Monowai. Results from direction‐of‐arrival calculations and density‐based spatial clustering indicate that 82 discrete episodes of activity occurred between July 2003 and March 2004, and from April 2014 to January 2017. Volcanic episodes are typically spaced days to weeks apart, range from hours to days in length, and amount to a cumulative sum of 137 days of arrivals in total, making Monowai one of the most active submarine arc volcanoes on Earth. The resolution of the hydrophone recordings surpasses broadband network data by at least one order of magnitude, identifying seismic events as low as 2.2 mb in the Kermadec Arc region. Further observations suggest volcanic activity at a location approximately 400 km north of Monowai in the Tonga Arc, and at Healy or Brothers volcano in the southern Kermadec Arc. Our findings are consistent with previous studies and highlight the exceptional capabilities of the IMS network for the scientific study of active volcanism in the global ocean. Supporting Information
- Published
- 2018
38. The use of object-oriented and process-oriented methods for gravity anomaly modelling of sedimentary basins
- Author
-
Anthony Watts
- Subjects
geography ,Object-oriented programming ,geography.geographical_feature_category ,010504 meteorology & atmospheric sciences ,Geophysics ,Sedimentary basin ,010502 geochemistry & geophysics ,01 natural sciences ,Gravity anomaly ,Geochemistry and Petrology ,Process oriented ,Lithospheric flexure ,Geology ,0105 earth and related environmental sciences - Abstract
Gravity anomalies have provided some of the most commonly accepted models we have for the density structure, stress state and strength of Earth's crust and lithosphere. Two approaches in the indirect approach to gravity interpretation have been followed. In one, Object-Oriented Gravity Modelling (OOGM), physical models are constructed for the geometry and density of a causative body and a ‘trial and error’ method is used to adjust the shape of a body until a satisfactory fit with observations is obtained. In another, Process-Oriented Gravity Modelling (POGM), one or more geological processes, such as sediment loading are considered, along with the density, and parameters such as the flexural rigidity of the lithosphere are varied until a fit is obtained. Both OOGM and POGM are based on the density structure and so should yield the same results. Curiously though, the two approaches have not yet been compared. We show here that in the case of a rifted continental margin that is subsequently loaded by sediment, OOGM and POGM do, in fact, yield the same gravity anomaly. Therefore, gravity anomalies yield information not only on the physical structure, but geological processes in the past. We attribute this to the presence of an elastic ‘core’ which, irrespective of yielding, imparts on the lithosphere a ‘memory’ and allows gravity measurements made today to be used to infer past geological events.
- Published
- 2018
39. Seismic and gravity constraints on flexural models for the origin of seaward dipping reflectors
- Author
-
RL Morgan and Anthony Watts
- Subjects
Gravity (chemistry) ,Geophysics ,010504 meteorology & atmospheric sciences ,Flexural strength ,Geochemistry and Petrology ,Lithospheric flexure ,010502 geochemistry & geophysics ,01 natural sciences ,Seismology ,Geology ,0105 earth and related environmental sciences - Abstract
Seaward dipping reflectors (SDRs) are ubiquitous features of the offshore regions of volcanic rifted continental margins where they comprise wedge-shaped packages of mainly extrusive lava flows. However, their origin has been disputed with some workers suggesting they form by progressive subsidence of extended crust while others propose they are accommodated within the crust by one or more continent-dipping normal faults. We present here a simple model in which SDRs are formed by a succession of dykes which intrude and load the crust. These loads cause a surface flexure, which is subsequently infilled and loaded by volcanic material. The model, which does not require a bounding normal fault, explains the arcuate shape, limited offlap geometries and downdip thickening of SDRs as observed in seismic reflection profile data. By comparing observed and calculated dips we are able to constrain the elastic plate model type and the effective elastic thickness of extended lithosphere, Te. Results suggest a broken plate or significantly weakened continuous plate model is required to produce the characteristic arcuate shape. Decreasing the Te for successive loads as rifting progresses produces offlap of subpackages, while increasing the Te produces onlap. We have verified our results using process-oriented gravity modelling, in which the gravity effect of surface volcanic infill loads is calculated and combined with the gravity effect of buried dyke loads and the gravity effect of their isostatic compensation. Results from a case study in the Orange Basin, offshore Namibia show good general agreement between observed Airy isostatic anomalies and calculated gravity anomalies with Te in the range 1–3 km. The steep gradient that is often observed in the Airy isostatic gravity anomaly at rifted margins is therefore a useful proxy for the seaward edge of the dykes that intrude the crust prior to seafloor spreading, rather than a change in basement elevation at the boundary between oceanic and continental crust, as had been proposed by previous workers.
- Published
- 2018
40. In Situ Study of the Function of Bacterioruberin in the Dual-Chromophore Photoreceptor Archaerhodopsin-4
- Author
-
Xin Zhao, Sijin Chen, Haolin Cui, Anthony Watts, Yanan Yang, Xiaoyan Ding, and Chao Sun
- Subjects
Halobacterium salinarum ,0301 basic medicine ,Archaeal Proteins ,Kinetics ,010402 general chemistry ,01 natural sciences ,Catalysis ,03 medical and health sciences ,chemistry.chemical_compound ,Adenosine Triphosphate ,Protein structure ,Isomerism ,Amino Acid Sequence ,Peptide sequence ,biology ,Protein Stability ,Chemistry ,Retinal ,General Medicine ,General Chemistry ,Chromophore ,biology.organism_classification ,Carotenoids ,0104 chemical sciences ,030104 developmental biology ,Biophysics ,Bacterial rhodopsins ,Protein Multimerization ,Sequence Alignment ,Adenosine triphosphate - Abstract
While certain archaeal ion pumps have been shown to contain two chromophores, retinal and the carotenoid bacterioruberin, the functions of bacterioruberin have not been well explored. To address this research gap, recombinant archaerhodopsin-4 (aR4), either with retinal only or with both retinal and bacterioruberin chromophores, was successfully expressed together with endogenous lipids in H. salinarum L33 and MPK409 respectively. In situ solid-state NMR, supported by molecular spectroscopy and functional assays, revealed for the first time that the retinal thermal equilibrium in the dark-adapted state is modulated by bacterioruberin binding through a cluster of aromatic residues on helix E. Bacterioruberin not only stabilizes the protein trimeric structure but also affects the photocycle kinetics and the ATP formation rate. These new insights may be generalized to other receptors and proteins in which metastable thermal equilibria and functions are perturbed by ligand binding.
- Published
- 2018
41. Cratonic basins and the Wilson cycle: a perspective from the Parnaíba Basin, Brazil
- Author
-
B. Tozer, M. C. Daly, and Anthony Watts
- Subjects
Paleontology ,010504 meteorology & atmospheric sciences ,Wilson cycle ,Perspective (graphical) ,Geology ,Ocean Engineering ,Structural basin ,010502 geochemistry & geophysics ,01 natural sciences ,0105 earth and related environmental sciences ,Water Science and Technology - Abstract
Cratonic basins appear to occupy a specific place in the Wilson cycle, initiating after continental collision and supercontinent development, but before rifting and continental break-up. They do not result directly from the horizontal plate motions characteristic of the Wilson cycle, but from localized, long-lived subsidence. Covering c. 10% of the Earth’s continental crust, most of the preserved cratonic basins developed in the Early Paleozoic after the formation of Gondwana and Laurentia. Recent investigation of the Parnaíba cratonic basin of Brazil has shown that this basin, and potentially cratonic basins in general, are characterized by six features: (1) formation on thickened lithosphere (>150 km); (2) a pronounced basal unconformity; (3) a subcircular outline and large area of 0.5 × 10^5 to 2 × 10^6 km^2; (4) long-lived (100–300 myr) quasi-exponential tectonic subsidence of shallow marine and terrestrial sediments; (5) no major extensional strain features, such as rifts, crustal or lithospheric thinning or Moho elevation; and (6) dense, high velocity and conductive lower crust and upper mantle. These characteristics indicate basin initiation and development by purely vertical subsidence of the lithosphere, either thermally or mechanically driven. Thermal subsidence may be related to orogenic thickening, radiogenic heating and erosion associated with supercontinent assembly, whereas mechanical subsidence may be a result of the emplacement in the lower crust or upper mantle of a dense igneous body related to plume activity during the lifetime of a supercontinent.
- Published
- 2018
42. Lateral Variations in Foreland Flexure of a Rifted Continental Margin: The Aquitaine Basin (SW France)
- Author
-
Paul Angrand, Mary Ford, and Anthony Watts
- Subjects
Paleontology ,Geophysics ,Rift ,010504 meteorology & atmospheric sciences ,Continental margin ,Geochemistry and Petrology ,Structural basin ,010502 geochemistry & geophysics ,01 natural sciences ,Foreland basin ,Geology ,0105 earth and related environmental sciences - Published
- 2018
43. Subsidence History and Seismic Stratigraphy of the Western Musandam Peninsula, Oman-United Arab Emirates Mountains
- Author
-
Michael P. Searle, Mohammed Y. Ali, S. Aidarbayev, and Anthony Watts
- Subjects
Paleontology ,geography ,Geophysics ,geography.geographical_feature_category ,Geochemistry and Petrology ,Peninsula ,Seismic stratigraphy ,Subsidence ,010503 geology ,010502 geochemistry & geophysics ,01 natural sciences ,Geology ,0105 earth and related environmental sciences - Published
- 2018
44. Cratonic basin formation: a case study of the Parnaíba Basin of Brazil
- Author
-
Reinhardt A. Fuck, M. C. Daly, J. Julià, David MacDonald, and Anthony Watts
- Subjects
010504 meteorology & atmospheric sciences ,Geochemistry ,Geology ,Ocean Engineering ,Structural basin ,010502 geochemistry & geophysics ,01 natural sciences ,0105 earth and related environmental sciences ,Water Science and Technology - Abstract
Cratonic basins comprise a significant component of the Earth's continental crust and surface geology. Their subcircular form and large areas of flat-lying, largely undeformed sedimentary rocks characterize the central regions of many continents, and are also a significant habitat for water, mineral and petroleum resources. These basinal regions have been extensively studied, yet there is little consensus on the driving mechanism of their subsidence or their greater tectonic context. Here we present the results of an integrated basin analysis of the Paleozoic–Early Mesozoic Parnaíba cratonic basin of NE Brazil. The analysis integrates existing geological and geophysical data, and a new deep-crustal geophysical dataset, to determine the deep structure of the basin and the underlying crust and mantle. Several major features have emerged from this which constrain the basins genesis: (1) continental–shallow-marine stratigraphy characterized by an exponentially decreasing tectonic subsidence with a relatively long time constant of the order of 70–90 myr; (2) a complex Proterozoic–Early Paleozoic basement that comprises at least three major crustal blocks defined by seismic facies and conductivity contrasts with no evidence of an extensive rift system beneath the basin; (3) a mid-crustal fabric that appears to define the top of a dense and seismically fast lower crust (Vp 6.7–6.8 km s−1 and Vs 3.7–3.8 km s−1) and upper mantle (Vp 8.2–8.4 km s−1) directly beneath the basin, and which correlates with a sediment-corrected Bouger gravity anomaly high of +40–60 mGal; (4) a Moho that is generally as deep or deeper beneath the basin (40–45 km) than its surrounding region (34–40 km), and which appears stepped at the terrane boundaries; (5) a relatively conductive crust and upper mantle beneath the basin, and relatively resistive crust along the boundaries of the basement blocks; and (6) igneous events immediately before and after formation of the cratonic megasequence and a geochemically enriched mantle beneath the basin that sourced two major episodes of Mesozoic igneous intrusions. These latter events are responsible for the development of an atypical gas-prone petroleum system dependent on local magmatic events for heat generation and trapping configurations. The data describing these features are presented and discussed, and their implications used to draw conclusions about the formation of the Parnaíba Basin specifically and cratonic basins more generally.
- Published
- 2018
45. Crustal structure of the Nogal basin, northern Somalia
- Author
-
Anthony Watts and Moamen Ali
- Subjects
Graben ,Paleontology ,Rift ,Continental crust ,Doming ,Geology ,Crust ,Cretaceous ,Gravity anomaly ,Bouguer anomaly ,Earth-Surface Processes - Abstract
Gravity, seismic and well data have been used to determine the crustal structure of the poorly-known Nogal basin, northern Somalia. Seismic data delineate a WNW-ESE trending graben infilled mainly by up to 6–7 km of Upper Cretaceous to Oligocene-Miocene sediments. Backstripping of well data show that the basin developed by thinning and rifting of continental crust during the Late Jurassic , Late Cretaceous and Oligocene . The Oligocene rift event is only observed at the centre of the basin, and correlates with the opening of the Gulf of Aden. The Late Jurassic rift event, which has been recognised in the northern Somalia, is largely absent in the basin. For the western part of the basin, Process Oriented Gravity and flexure Modelling (POGM) suggest a best-fit Te of 5 km, which explains both the amplitude and wavelength of the observed free-air gravity anomaly . However, the modelled anomaly in the eastern part of the basin is 30–40 mGal higher than the observed. Sediment-corrected Bouguer gravity anomalies show that the basin is associated with a relative high, which increases in amplitude to the east, towards the Kalis-1 well. We, therefore, propose that the eastern part of the basin to be locally intruded by dense magmatic material in the lower crust and/or upper mantle , which have elevated the gravity. The amount of crustal thinning inferred at Kalis-1 and Nogal-1 wells from backstripping is consistent with the results of POGM and flexure modelling. The models suggest the crust thins from about 35 km beneath the basin flanks to 32.6 km and 27.2 km at the Kalis-1 and Nogal-1 wells respectively. Moreover, the models suggest that Late Jurassic rifting was limited to the western part of the basin. The comparison of the long wavelength free-air gravity anomaly with the gravity effect of the topography based on different gravity/topography ratios suggest that while the crust is locally thinned beneath the basin it is also regionally domed, possibly by flexure due to magmatic intrusion. The doming predates the Late Cretaceous rifting and coincides with the same pre-Cenomanian uplift event during which substantial thicknesses of Upper Jurassic and Lower Cretaceous sediments were exhumed.
- Published
- 2021
46. From Extension to Shortening: Tectonic Inversion Distributed in Time and Space in the Alboran Sea, Western Mediterranean
- Author
-
Anthony Watts, Menchu Comas, Lidia Lonergan, and Pedro Martínez-García
- Subjects
geography ,geography.geographical_feature_category ,Rift ,010504 meteorology & atmospheric sciences ,Continental crust ,Inversion (geology) ,Crust ,010502 geochemistry & geophysics ,Strike-slip tectonics ,01 natural sciences ,Volcanic rock ,Tectonics ,Geophysics ,Geochemistry and Petrology ,Sedimentary basin analysis ,Geology ,Seismology ,0105 earth and related environmental sciences - Abstract
2D seismic reflection data tied to biostratigraphical and log information from wells in the central and south-eastern Alboran Sea have allowed us to constrain the spatial and temporal distribution of rifting and inversion. Normal faults, tilted basement blocks and growth wedges reveal a thinned continental crust that formed in response to NW-SE extension. To the east a secondary SW-NE trend of extension affects the transitional crust adjacent to the oceanic Algerian Basin. The maximum thickness of syn-rift sediments is ~3.5 km and the oldest recorded deposits are Serravallian. The WNW-ESE Yusuf fault formed a buttress separating and accommodating variable extension between two different tectonic domains: the thinned continental crust of Alboran and the oceanic spreading of the Algerian Basin. Late Tortonian to present-day NW-SE Africa/Eurasia plate convergence drove shortening and reactivation of some of the earlier extensional structures as reverse and strike-slip faults, forming complex, compartmentalised sub-basins. Tectonic inversion coexisted with the formation of new faults and folds. Inversion was partial along the Habibas Basin and Al-Idrisi fault, but complete along the Alboran Ridge, where some SW-NE trending faults were perpendicular to the recent NW-SE plate convergence and were reactivated as thrusts. The WNW-ESE Yusuf fault is oblique to the convergence vector and therefore, reactivation is mainly expressed as transpressional deformation. Volcanic rocks intruded along the Alboran Ridge and Yusuf faults during the latest stages of extension, formed rheological anisotropies that localised the later inversion.
- Published
- 2017
47. Structures of the archaerhodopsin-3 transporter reveal that disordering of internal water networks underpins receptor sensitization
- Author
-
Isabel Moraes, Peter J. Judge, Juan F. Bada Juarez, Danny Axford, Tristan Kwan, and Anthony Watts
- Subjects
Inorganic Chemistry ,Structural Biology ,General Materials Science ,Physical and Theoretical Chemistry ,Condensed Matter Physics ,Biochemistry - Published
- 2021
48. Flexural Isostasy: Constraints From Gravity and Topography Power Spectra
- Author
-
James D P Moore and Anthony Watts
- Subjects
Convection ,010504 meteorology & atmospheric sciences ,Spherical harmonics ,Geophysics ,010502 geochemistry & geophysics ,Geodesy ,01 natural sciences ,Mantle (geology) ,Gravity anomaly ,Physics::Geophysics ,Tectonics ,Flexural strength ,Gravitational field ,Space and Planetary Science ,Geochemistry and Petrology ,Isostasy ,Earth and Planetary Sciences (miscellaneous) ,Physics::Atmospheric and Oceanic Physics ,Geology ,0105 earth and related environmental sciences - Abstract
We have used spherical harmonic coefficients that describe Earth's gravity anomaly and topography fields to quantify the role of isostasy in contributing to crustal and upper mantle structure. Power spectra reveal that the gravity effect of topography and its flexural compensation contributes significantly to the observed free-air gravity anomaly spectra for spherical harmonic degree 33 400) and lower (n < 33) degrees, but topography appears either uncompensated or fully compensated at these degrees, irrespective of the actual Te. All isostatic models underpredict the spectra at 2 < n < 12 and so we interpret the low order Earth's gravity field as caused, at least in part, by non-isostatic processes due to dynamic motions such as those associated with convective upwellings and downwellings in Earth's mantle.
- Published
- 2017
49. Crustal structure, gravity anomalies, and subsidence history of the Parnaíba cratonic basin, Northeast Brazil
- Author
-
Anthony Watts, B. Tozer, and M. C. Daly
- Subjects
Tectonic subsidence ,geography ,geography.geographical_feature_category ,010504 meteorology & atmospheric sciences ,Subsidence ,Structural basin ,Sedimentary basin ,010502 geochemistry & geophysics ,01 natural sciences ,Gravity anomaly ,Paleontology ,Tectonics ,Geophysics ,Space and Planetary Science ,Geochemistry and Petrology ,Lithosphere ,Earth and Planetary Sciences (miscellaneous) ,Sedimentary basin analysis ,Seismology ,Geology ,0105 earth and related environmental sciences - Abstract
Cratonic basins cover more than 10p of Earth's continental surface area, yet their origin remains enigmatic. In this thesis a suite of new and legacy geophysical and geological data are integrated to constrain the origin of the Parnaiba basin, a cratonic basin in Northeast Brazil. These data include a 1400 km long, deep (20 s two-way travel time) seismic reflection profile, five +/- 110 km offset wide-angle split-spread receiver gathers, gravity anomaly, and well data. In the centre of the basin, the depth to pre-Paleozoic basement is T 3.3 km, a zone of midcrustal reflectivity (MCR) can be traced laterally for T 250 km at depths between 17-25 km and Moho depth is T 42 +/- 2 km . Gravity and P-wave modelling suggests that the MCR represents the upper surface of a high density (2985 kg m 3 ) and V p (6.7–7.0 km s -1 ) lower crustal body, likely of magmatic origin. Backstripping of well data shows a concave up decreasing tectonic subsidence, similar in form to that commonly observed in rift-type basins. It is shown, however, that the seismic and gravity data are inconsistent with an extensional origin. It is shown that an intrusive body in the lower crust that has loaded and flexed the surface of the crust, combined with sediment loading, provides a satisfactory fit to the observed gravity anomaly, sediment thickness and basin shape. A buried load model is also consistent with seismic data, which suggest that the Moho is as deep or deeper beneath the basin centre than its flanks and accounts for at least part of the tectonic subsidence through a viscoelastic stress relaxation that occurs in the lithosphere following load emplacement. Comparative analysis of the Michigan and Congo basins shows gravity data from these basins is also consistent with a lower crustal mass excess, while subsidence analysis shows viscoelastic stress relaxation may also contribute to their early subsidence histories. However, unlike Parnaiba, both of these basins appear to have been subjected to secondary tectonic processes that obscure the primary 'cratonic basin' subsidence signals. Parnaiba basin, therefore, offers an excellent record for the investigation of cratonic basin formation.
- Published
- 2017
50. Engineering monolayer poration for rapid exfoliation of microbial membranes
- Author
-
Angelo Bella, Isabel Bennett, Eleonora Cerasoli, Jason Crain, André Henrion, Anthony Watts, Alice L. B. Pyne, Anita Roethke, Chris R. M. Grovenor, Nilofar Faruqui, Santanu Ray, Jascindra Ravi, Haibo Jiang, Daniel Yin, Marc Philipp Pfeil, Peter J. Judge, Juan C. Muñoz-García, Baptiste Lamarre, Bart W. Hoogenboom, Patrizia Iavicoli, Luigi Calzolai, Maxim G. Ryadnov, Benjamin Little, Bernd Reisinger, and Glenn J. Martyna
- Subjects
0301 basic medicine ,biology ,Phospholipid ,General Chemistry ,Antimicrobial ,biology.organism_classification ,Combinatorial chemistry ,Bacterial cell structure ,Transmembrane protein ,Chemistry ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,Membrane ,chemistry ,Monolayer ,Biophysics ,Structural motif ,Bacteria - Abstract
A novel mechanism of monolayer poration leading to the rapid exfoliation and lysis of microbial membranes is reported., The spread of bacterial resistance to traditional antibiotics continues to stimulate the search for alternative antimicrobial strategies. All forms of life, from bacteria to humans, are postulated to rely on a fundamental host defense mechanism, which exploits the formation of open pores in microbial phospholipid bilayers. Here we predict that transmembrane poration is not necessary for antimicrobial activity and reveal a distinct poration mechanism that targets the outer leaflet of phospholipid bilayers. Using a combination of molecular-scale and real-time imaging, spectroscopy and spectrometry approaches, we introduce a structural motif with a universal insertion mode in reconstituted membranes and live bacteria. We demonstrate that this motif rapidly assembles into monolayer pits that coalesce during progressive membrane exfoliation, leading to bacterial cell death within minutes. The findings offer a new physical basis for designing effective antibiotics.
- Published
- 2017
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