Search

Your search keyword '"Olivia Berthoumieu"' showing total 10 results
Start Over Author "Olivia Berthoumieu"
10 results on '"Olivia Berthoumieu"'

1. Deciphering the structure, growth and assembly of amyloid-like fibrils using high-speed atomic force microscopy.

Author

Pierre-Emmanuel Milhiet, Daisuke Yamamoto, Olivia Berthoumieu, Patrice Dosset, Christian Le Grimellec, Jean-Michel Verdier, Stéphane Marchal, and Toshio Ando

Subjects
Medicine, Science
Abstract

Formation of fibrillar structures of proteins that deposit into aggregates has been suggested to play a key role in various neurodegenerative diseases. However mechanisms and dynamics of fibrillization remains to be elucidated. We have previously established that lithostathine, a protein overexpressed in the pre-clinical stages of Alzheimer's disease and present in the pathognomonic lesions associated with this disease, form fibrillar aggregates after its N-terminal truncation. In this paper we visualized, using high-speed atomic force microscopy (HS-AFM), growth and assembly of lithostathine protofibrils under physiological conditions with a time resolution of one image/s. Real-time imaging highlighted a very high velocity of elongation. Formation of fibrils via protofibril lateral association and stacking was also monitored revealing a zipper-like mechanism of association. We also demonstrate that, like other amyloid ß peptides, two lithostathine protofibrils can associate to form helical fibrils. Another striking finding is the propensity of the end of a growing protofibril or fibril to associate with the edge of a second fibril, forming false branching point. Taken together this study provides new clues about fibrillization mechanism of amyloid proteins.

Published
2010
Full Text
View/download PDF

2. Why Is Research on Amyloid-β Failing to Give New Drugs for Alzheimer's Disease?

Author

Maria P. del Castillo-Frias, Olivia Berthoumieu, Andrew J. Doig, Nigel M. Hooper, Jessica Nasica-Labouze, Philippe Derreumaux, Peter Faller, Fabio Sterpone, Bogdan Tarus, and Phuong H. Nguyen

Subjects
0301 basic medicine, Physiology, Cognitive Neuroscience, In silico, Tau protein, amyloid-β, Biochemistry, drugs, 03 medical and health sciences, 0302 clinical medicine, In vivo, Alzheimer Disease, Drug Discovery, Medicine, Animals, Humans, Amyloid beta-Peptides, biology, business.industry, P3 peptide, Cell Biology, General Medicine, Small molecule, In vitro, in vitro and in vivo studies, Biochemistry of Alzheimer's disease, 030104 developmental biology, Neuroprotective Agents, biology.protein, Antibody, business, Neuroscience, Alzheimer’s disease, 030217 neurology & neurosurgery, Computer simulations
Abstract

The two hallmarks of Alzheimer’s disease (AD) are the presence of neurofibrillary tangles (NFT) made of aggregates of the hyperphosphorylated tau protein and of amyloid plaques composed of amyloid-β (Aβ) peptides, primarily Aβ1–40 and Aβ1–42. Targeting the production, aggregation, and toxicity of Aβ with small molecule drugs or antibodies is an active area of AD research due to the general acceptance of the amyloid cascade hypothesis, but thus far all drugs targeting Aβ have failed. From a review of the recent literature and our own experience based on in vitro, in silico, and in vivo studies, we present some reasons to explain this repetitive failure.

Published
2017
Full Text
View/download PDF

3. Molecular scale conductance photoswitching in engineered bacteriorhodopsin

Author

Amol V. Patil, Lubica Aslimovska, Jason J. Davis, Olivia Berthoumieu, Wang Xi, and Anthony Watts

Subjects
Halobacterium salinarum, Models, Molecular, Bioengineering, Microscopy, Atomic Force, Protein Engineering, Photochemistry, Nanotechnology, General Materials Science, Surface plasmon resonance, Electrodes, Voltammetry, Nanodevice, biology, Chemistry, Mechanical Engineering, Electric Conductivity, Conductance, Bacteriorhodopsin, General Chemistry, Surface Plasmon Resonance, Photochemical Processes, Condensed Matter Physics, Crystallography, Membrane, Chemisorption, Covalent bond, Bacteriorhodopsins, biology.protein, Gold
Abstract

Bacteriorhodopsin (BR) is a robust light-driven proton pump embedded in the purple membrane of the extremophilic archae Halobacterium salinarium. Its photo- activity remains in the dry state, making BR of significant interest for nanotechnological use. Here, in a novel configuration, BR was depleted from most of its endogenous lipids and covalently and asymmetrically anchored onto a gold electrode through a strategically located and highly responsive cysteine mutation; BR has no indigenous cysteines. Chemisorption on gold was characterized by surface plasmon resonance, reductive striping voltammetry, ellipsometry, and atomic force microscopy (AFM). For the first time, the conductance of isolated protein trimers, intimately probed by conducting AFM, was reproducibly and reversibly switched under wavelength-specific conditions (mean resistance of 39 ± 12 MΩ under illumination, 137 ± 18 MΩ in the dark), demonstrating a surface stability that is relevant to potential nanodevice applications.

Published
2016
Full Text
View/download PDF

4. Engineered bacteriorhodopsin: a molecular scale potential switch

Author

Olivia Berthoumieu, Thenuhan Premaraban, Anthony Watts, Jason J. Davis, and Amol V. Patil

Subjects
Halobacterium salinarum, Models, Molecular, Protein Conformation, Microscopy, Atomic Force, Protein Engineering, Catalysis, Metal, Monolayer, Microscopy, Point Mutation, Cysteine, Electrodes, Kelvin probe force microscope, chemistry.chemical_classification, biology, Chemistry, Biomolecule, Organic Chemistry, Bacteriorhodopsin, General Chemistry, Protein engineering, Crystallography, Immobilized Proteins, Covalent bond, visual_art, Bacteriorhodopsins, visual_art.visual_art_medium, biology.protein, Biophysics, Protein Multimerization, Protons
Abstract

Bacteriorhodopsin, BR, is a natural, photoresponsive, biomolecule that has potential application in data storage, imaging and sensing. Being membrane-bound, however, it is coupled with metallic electronic surfaces only with some difficulty. We report herein a facile method to generate uniformly orientated, anchored and active monolayers of BR on metallic electrodes. In the present study, the cytoplasmic side of the BR is equipped with an engineered cysteine to achieve largely lipid-free, orientation-specific, highly stable, covalent immobilization on gold surfaces. By using non-invasive Kelvin probe force microscopy, it is possible to measure the light-induced proton accumulation at the extracellular protein surface at truly molecular scales. The intimate probe-BR interaction possible on lipid removal facilitates the detection of photoinduced surface potential switching substantially larger ((20.4 ± 7.5) mV) with functional single delipidated mutant BR trimers than for the wild-type protein. The proton pumping detected is also notably highly unidirectional with the orientated protein.

Published
2016
Full Text
View/download PDF

5. P1‐039: Inhibitors of amyloid beta peptide aggregation: Toward new drugs against Alzheimer's disease

Author

Olivia Berthoumieu, Peter Faller, Philippe Derreumaux, and Andrew J. Doig

Subjects
chemistry.chemical_classification, biology, Epidemiology, Amyloid beta, Chemistry, Health Policy, P3 peptide, Peptide, Disease, Pharmacology, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, biology.protein, Neurology (clinical), Geriatrics and Gerontology
Published
2015
Full Text
View/download PDF

6. Molecular structure of the NQTrp inhibitor with the Alzheimer A beta 1-28 monomer

Author

Peter Faller, Bogdan Tarus, Olivia Berthoumieu, Philippe Derreumaux, Andrew J. Doig, Phuong H. Nguyen, Unité de recherche Virologie et Immunologie Moléculaires (VIM), Institut National de la Recherche Agronomique (INRA), Laboratoire de biochimie théorique [Paris] (LBT (UPR_9080)), Université Paris Diderot - Paris 7 (UPD7)-Institut de biologie physico-chimique (IBPC), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), University of Manchester [Manchester], Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Institut de biologie physico-chimique (IBPC (FR_550)), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut de biologie physico-chimique (IBPC), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Protein Folding, Dimer, Population, Peptide, Molecular Dynamics Simulation, Protein Structure, Secondary, Molecular dynamics, chemistry.chemical_compound, Drug Discovery, Humans, Senile plaques, education, Protein secondary structure, ComputingMilieux_MISCELLANEOUS, Pharmacology, chemistry.chemical_classification, education.field_of_study, Amyloid beta-Peptides, Organic Chemistry, Tryptophan, General Medicine, Small molecule, Peptide Fragments, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Crystallography, Kinetics, Monomer, chemistry, Biophysics, Thermodynamics, Protein Multimerization, Naphthoquinones, Protein Binding
Abstract

The self-assembly of the amyloid-β (Aβ) peptide of various amino acid lengths into senile plaques is one hallmark of Alzheimer's disease pathology. In the past decade, many small molecules, including NQTrp, have been identified to reduce aggregation and toxicity. However, due to the heterogeneity of the conformational ensemble of Aβ with drugs, we lack detailed structures of the transient complexes. Following our previous simulation of the monomer of Aβ1-28, here we characterize the equilibrium ensemble of the Aβ1-28 monomer with NQTrp by means of extensive atomistic replica exchange molecular dynamics simulations using a force field known to fold diverse proteins correctly. While the secondary structure content and the intrinsic disorder of the whole peptides are very similar and the lifetimes of the salt-bridges remain constant, the population of β-hairpin is reduced by a factor of 1.5 and the population of α-helix in the region 17–24 is increased by a factor of two upon NQTrp binding. These two factors, which impact the free energy barrier for nucleation, provide a first explanation for the reported reduced Aβ1-40/1-42 aggregation kinetics in the presence of NQTrp. Backbone and side-chain interactions of Aβ with NQTrp may also inhibit Aβ–Aβ contacts. The fraction of free Aβ1-28 monomer is, however, on the order of 20–25% at 17.5 mM, and this shows that the affinity of NQTrp is low and hence its inhibitory activity is not very strong. This inhibitor can be improved to reduce the formation of dimer, a critical step in aggregation and toxicity.

Published
2015
Full Text
View/download PDF

7. Combined Experimental and Simulation Studies Suggest a Revised Mode of Action of the Anti-Alzheimer Disease Drug NQ-Trp

Author

Sabrina Noël, Bogdan Tarus, Claire Rampon, Andrew J. Doig, Phuong H. Nguyen, Philippe Derreumaux, Maria P. del Castillo-Frias, Sabrina Ferre, Olivier Saurel, Peter Faller, Jessica Nasica-Labouze, Olivia Berthoumieu, Unité de recherche Virologie et Immunologie Moléculaires (VIM), Institut National de la Recherche Agronomique (INRA), Institut de physiologie et biologie cellulaires (IPBC), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches sur la Cognition Animale (CRCA), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de biochimie théorique [Paris] (LBT (UPR_9080)), Centre National de la Recherche Scientifique (CNRS)-Institut de biologie physico-chimique (IBPC), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Institut de biologie physico-chimique (IBPC), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut des sciences du cerveau de Toulouse. (ISCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Institut de biologie physico-chimique (IBPC (FR_550)), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Fluorophore, Magnetic Resonance Spectroscopy, Context (language use), Peptide, Molecular Dynamics Simulation, Catalysis, chemistry.chemical_compound, In vivo, Alzheimer Disease, Humans, Binding site, Mode of action, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, Amyloid beta-Peptides, Chemistry, Organic Chemistry, Tryptophan, General Chemistry, Small molecule, Peptide Fragments, 3. Good health, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Monomer, Biochemistry, Naphthoquinones
Abstract

Inhibition of the aggregation of the monomeric peptide β-amyloid (Aβ) into oligomers is a widely studied therapeutic approach in Alzheimer's disease (AD). Many small molecules have been reported to work in this way, including 1,4-naphthoquinon-2-yl-L-tryptophan (NQ-Trp). NQ-Trp has been reported to inhibit aggregation, to rescue cells from Aβ toxicity, and showed complete phenotypic recovery in an in vivo AD model. In this work we investigated its molecular mechanism by using a combined approach of experimental and theoretical studies, and obtained converging results. NQ-Trp is a relatively weak inhibitor and the fluorescence data obtained by employing the fluorophore widely used to monitor aggregation into fibrils can be misinterpreted due to the inner filter effect. Simulations and NMR experiments showed that NQ-Trp has no specific "binding site"-type interaction with mono- and dimeric Aβ, which could explain its low inhibitory efficiency. This suggests that the reported anti-AD activity of NQ-Trp-type molecules in in vivo models has to involve another mechanism. This study has revealed the potential pitfalls in the development of aggregation inhibitors for amyloidogenic peptides, which are of general interest for all the molecules studied in the context of inhibiting the formation of toxic aggregates.

Published
2015
Full Text
View/download PDF

8. Role of metal ions in the self-assembly of the Alzheimer's amyloid-beta peptide

Author

Christelle Hureau, Peter Faller, Olivia Berthoumieu, Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Amyloid, Metal ions in aqueous solution, Inorganic chemistry, Kinetics, Nucleation, chemistry.chemical_element, Peptide, Zinc, 010402 general chemistry, 01 natural sciences, Ion, Inorganic Chemistry, 03 medical and health sciences, Alzheimer Disease, Humans, Physical and Theoretical Chemistry, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Amyloid beta-Peptides, Precipitation (chemistry), Hydrogen-Ion Concentration, Copper, 0104 chemical sciences, chemistry, Biophysics
Abstract

0020-1669; Aggregation of amyloid-beta (A beta) by self-assembly into oligomers or amyloids is a central event in Alzheimer's disease. Coordination of transition-metal ions, mainly copper and zinc, to A beta occurs in vivo and modulates the aggregation process. A survey of the impact of CuII and ZnII on the aggregation of A beta reveals some general trends: (i) ZnII and CuII at high micromolar concentrations and/or in a large superstoichiometric ratio compared to A beta have a tendency to promote amorphous aggregations (precipitation) over the ordered formation of fibrillar amyloids by self-assembly; (ii) metal ions affect the kinetics of A beta aggregations, with the most significant impact on the nucleation phase; (iii) the impact is metal-specific; (iv) CuII and ZnII affect the concentrations and/or the types of aggregation intermediates formed; (v) the binding of metal ions changes both the structure and the charge of A beta. The decrease in the overall charge at physiological pH increases the overall driving force for aggregation but may favor more precipitation over fibrillation, whereas the induced structural changes seem more relevant for the amyloid formation.

Published
2013
Full Text
View/download PDF

9. Enhanced photocurrent in engineered bacteriorhodopsin monolayer

Author

Amol V. Patil, Olivia Berthoumieu, Anthony Watts, Thenhuan Premaruban, and Jason J. Davis

Subjects
Static Electricity, Photodetector, Nanotechnology, Microscopy, Atomic Force, Metal, Monolayer, Materials Chemistry, Solar Energy, Cysteine, Physical and Theoretical Chemistry, Electrodes, Photocurrent, Photons, biology, business.industry, Chemistry, Bacteriorhodopsin, Transmembrane protein, Surfaces, Coatings and Films, Amino Acid Substitution, visual_art, Bacteriorhodopsins, Electrode, Mutation, visual_art.visual_art_medium, biology.protein, Optoelectronics, Molecular Density, business
Abstract

The integration of the transmembrane protein bacteriorhodopsin (BR) with man-made electrode surfaces has attracted a great deal of interest for some two decades or more and holds significant promise from the perspective of derived photoresponse or energy capture interfaces. Here we demonstrate that a novel and strategically engineered cysteine site (M163C) can be used to intimately and effectively couple delipidated BR to supporting metallic electrode surfaces. By virtue of the combined effects of the greater surface molecular density afforded by delipidation, and the vicinity of the electrostatic changes associated with proton pumping to the transducing metallic continuum, the resulting films generate a considerably greater photocurrent density on wavelength-selective illumination than previously achievable with monolayers of BR. Given the uniquely photoresponsive, wavelength-selective, and photostable characteristics of this protein, the work has implications for utilization in solar energy capture and photodetector devices.

Published
2011

10. Deciphering the Structure, Growth and Assembly of Amyloid-Like Fibrils Using High-Speed Atomic Force Microscopy

Author

Jean-Michel Verdier, Toshio Ando, Patrice Dosset, Christian Le Grimellec, Pierre-Emmanuel Milhiet, Stéphane Marchal, Daisuke Yamamoto, Olivia Berthoumieu, 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), Mécanismes moléculaires dans les démences neurodégénératives (MMDN), Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École pratique des hautes études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)

Subjects
Amyloid, CALCIUM-CARBONATE, ALPHA-SYNUCLEIN, Globular protein, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, HUMAN LITHOSTATHINE, Biophysics, lcsh:Medicine, 02 engineering and technology, macromolecular substances, Microscopy, Atomic Force, Fibril, Biochemistry/Protein Folding, law.invention, 03 medical and health sciences, chemistry.chemical_compound, Protein structure, law, Lithostathine, Microscopy, CRYSTAL-STRUCTURE, lcsh:Science, 030304 developmental biology, PROTEIN FIBRILS, Alpha-synuclein, chemistry.chemical_classification, 0303 health sciences, Multidisciplinary, Molecular Structure, PAIRED HELICAL FILAMENTS, lcsh:R, IN-VITRO, 021001 nanoscience & nanotechnology, SUPRAMOLECULAR ASSEMBLIES, Neurological Disorders/Prion Diseases, ALZHEIMERS-DISEASE, chemistry, BIOMOLECULAR PROCESSES, Biophysics/Experimental Biophysical Methods, lcsh:Q, Electron microscope, 0210 nano-technology, Neurological Disorders/Alzheimer Disease, Research Article
Abstract

金沢大学理工研究域数物科学系, Formation of fibrillar structures of proteins that deposit into aggregates has been suggested to play a key role in various neurodegenerative diseases. However mechanisms and dynamics of fibrillization remains to be elucidated. We have previously established that lithostathine, a protein overexpressed in the pre-clinical stages of Alzheimer's disease and present in the pathognomonic lesions associated with this disease, form fibrillar aggregates after its N-terminal truncation. In this paper we visualized, using high-speed atomic force microscopy (HS-AFM), growth and assembly of lithostathine protofibrils under physiological conditions with a time resolution of one image/s. Real-time imaging highlighted a very high velocity of elongation. Formation of fibrils via protofibril lateral association and stacking was also monitored revealing a zipper-like mechanism of association. We also demonstrate that, like other amyloid ß peptides, two lithostathine protofibrils can associate to form helical fibrils. Another striking finding is the propensity of the end of a growing protofibril or fibril to associate with the edge of a second fibril, forming false branching point. Taken together this study provides new clues about fibrillization mechanism of amyloid proteins. © 2010 Milhiet et al.

Published
2010
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results