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725 results on '"Bond, Peter J."'

102. Molecular dynamics simulations of GlpF in micelle vs in a bilayer: Conformational dynamics of a membrane protein as a function of environment

Author

Patargias, George, Bond, Peter J., Deol, Sundeep S., and Sansom, Mark S.P.

Subjects
Micelles -- Research, Membrane proteins -- Chemical properties, Molecular dynamics -- Research, Chemicals, plastics and rubber industries
Abstract

An alpha-helical membrane protein, GlpF, in octyl glucoside (OG) micelles and in DMPC bilayers is explored to better understand the nature of protein-OG interactions, molecular dynamics simulations. OG is a detergent widely employed in structural and functional studies of membrane proteins.

Published
2005

123. The disordered plant dehydrin Lti30 protects the membrane during water-related stress by cross-linking lipids

Author

Gupta, Anjali, Marzinek, Jan K., Jefferies, Damien, Bond, Peter J., Harryson, Pia, Wohland, Thorsten, Gupta, Anjali, Marzinek, Jan K., Jefferies, Damien, Bond, Peter J., Harryson, Pia, and Wohland, Thorsten

Abstract

Dehydrins are intrinsically disordered proteins, generally expressed in plants as a response to embryogenesis and water-related stress. Their suggested functions are in membrane stabilization and cell protection. All dehydrins contain at least one copy of the highly conserved K-segment, proposed to be a membrane-binding motif. The dehydrin Lti30 (Arabidopsis thaliana) is up-regulated during cold and drought stress conditions and comprises six K-segments, each with two adjacent histidines. Lti30 interacts with the membrane electrostatically via pH-dependent protonation of the histidines. In this work, we seek a molecular understanding of the membrane interaction mechanism of Lti30 by determining the diffusion and molecular organization of Lti30 on model membrane systems by imaging total internal reflection- fluorescence correlation spectroscopy (ITIR-FCS) and molecular dynamics (MD) simulations. The dependence of the diffusion coefficient explored by ITIR-FCS together with MD simulations yields insights into Lti30 binding, domain partitioning, and aggregation. The effect of Lti30 on membrane lipid diffusion was studied on fluorescently labeled supported lipid bilayers of different lipid compositions at mechanistically important pH conditions. In parallel, we compared the mode of diffusion for short individual K-segment peptides. The results indicate that Lti30 binds the lipid bilayer via electrostatics, which restricts the mobility of lipids and bound protein molecules. At low pH, Lti30 binding induced lipid microdomain formation as well as protein aggregation, which could be correlated with one another. Moreover, at physiological pH, Lti30 forms nanoscale aggregates when proximal to the membrane suggesting that Lti30 may protect the cell by cross-linking the membrane lipids.

Published
2019
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124. Multiscale modeling of innate immune receptors:Endotoxin recognition and regulation by host defense peptides

Author

Holdbrook, Daniel A., Huber, Roland G., Marzinek, Jan K., Stubbusch, Astrid, Schmidtchen, Artur, Bond, Peter J., Holdbrook, Daniel A., Huber, Roland G., Marzinek, Jan K., Stubbusch, Astrid, Schmidtchen, Artur, and Bond, Peter J.

Abstract

The innate immune system provides a first line of defense against foreign microorganisms, and is typified by the Toll-like receptor (TLR) family. TLR4 is of particular interest, since over-stimulation of its pathway by excess lipopolysaccharide (LPS) molecules from the outer membranes of Gram-negative bacteria can result in sepsis, which causes millions of deaths each year. In this review, we outline our use of molecular simulation approaches to gain a better understanding of the determinants of LPS recognition, towards the search for novel immunotherapeutics. We first describe how atomic-resolution simulations have enabled us to elucidate the regulatory conformational changes in TLR4 associated with different LPS analogues, and hence a means to rationalize experimental structure-activity data. Furthermore, multiscale modelling strategies have provided a detailed description of the thermodynamics and intermediate structures associated with the entire TLR4 relay which consists of a number of transient receptor/coreceptor complexes allowing us trace the pathway of LPS transfer from bacterial membranes to the terminal receptor complex at the plasma membrane surface. Finally, we describe our efforts to leverage these computational models, in order to elucidate previously undisclosed anti-inflammatory mechanisms of endogenous host-defense peptides found in wounds. Collectively, this work represents a promising avenue for the development of novel anti-septic treatments, inspired by nature's innate defense strategies.

Published
2019

132. A T164S mutation in the dengue virus NS1 protein is associated with greater disease severity in mice

Author

Chan, Kitti Wing Ki, primary, Watanabe, Satoru, additional, Jin, Jocelyn Y., additional, Pompon, Julien, additional, Teng, Don, additional, Alonso, Sylvie, additional, Vijaykrishna, Dhanasekaran, additional, Halstead, Scott B., additional, Marzinek, Jan K., additional, Bond, Peter J., additional, Burla, Bo, additional, Torta, Federico, additional, Wenk, Markus R., additional, Ooi, Eng Eong, additional, and Vasudevan, Subhash G., additional

Published
2019
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137. Mechanism of Enhanced Immature Dengue Virus Attachment to Endosomal Membrane Induced by prM Antibody

Author

Wirawan, Melissa, primary, Fibriansah, Guntur, additional, Marzinek, Jan K., additional, Lim, Xin Xiang, additional, Ng, Thiam-Seng, additional, Sim, Adelene Y.L., additional, Zhang, Qian, additional, Kostyuchenko, Victor A., additional, Shi, Jian, additional, Smith, Scott A., additional, Verma, Chandra S., additional, Anand, Ganesh, additional, Crowe, James E., additional, Bond, Peter J., additional, and Lok, Shee-Mei, additional

Published
2019
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139. Directing GDNF-mediated neuronal signaling with proactively programmable cell-surface saccharide-free glycosaminoglycan mimetics

Author

Cai, Shuting, primary, Lukamto, Daniel H., additional, Toh, Jerry K. C., additional, Huber, Roland G., additional, Bond, Peter J., additional, Jee, Joo-Eun, additional, Lim, Teck Chuan, additional, Liu, Pei, additional, Chen, Liwei, additional, Qu, Qianqian Vicky, additional, Lee, Su Seong, additional, and Lee, Song-Gil, additional

Published
2019
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143. Influence of pH on the activity of thrombin-derived antimicrobial peptides

Author

Holdbrook, Daniel A., Singh, Shalini, Choong, Yeu Khai, Petrlova, Jitka, Malmsten, Martin, Bond, Peter J., Verma, Navin Kumar, Schmidtchen, Artur, Saravanan, Rathi, Holdbrook, Daniel A., Singh, Shalini, Choong, Yeu Khai, Petrlova, Jitka, Malmsten, Martin, Bond, Peter J., Verma, Navin Kumar, Schmidtchen, Artur, and Saravanan, Rathi

Abstract

The wound environment is characterized by physiological pH changes. Proteolysis of thrombin by wound-derived proteases, such as neutrophil elastase, generates antimicrobial thrombin-derived C-terminal peptides (TCPs), such as HVF18 (HVFRLKKWIQKVIDQFGE). Presence of such TCPs in human wound fluids in vivo, as well as the occurrence of an evolutionarily conserved His residue in the primary amino acid sequence of TCPs, prompted us to investigate the pH-dependent antibacterial action of HVF18, as well as of the prototypic GKY25 (GKYGFYTHVFRLKKWIQKVIDQFGE). We show that protonation of this His residue at pH 5.5 increases the antibacterial activity of both TCPs against Gram-negative Escherichia coil by membrane disruption. Physiological salt level (150 mM NaCI) augments antibacterial activity of GKY25 but diminishes for the shorter HVF18. Replacing His with Leu or Ser in GKY25 abolishes the His protonation-dependent increase in antibacterial activity at pH 5.5, whereas substitution with Lys maintains activity at neutral (pH 7.4) and acidic pH. Interestingly, both TCPs display decreased binding affinities to human CD14 with decreasing pH, suggesting a likely switch in mode-of-action, from anti-inflammatory at neutral pH to antibacterial at acidic pH. Together, the results demonstrate that apart from structural prerequisites such as peptide length, charge, and hydrophobicity, the evolutionarily conserved His residue of TCPs influences their antibacterial effects and reveals a previously unknown aspect of TCPs biological action.

Published
2018
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144. Protein-protein interactions in paralogues: Electrostatics modulates specificity on a conserved steric scaffold

Author

Ivanov, Stefan, Cawley, Andrew, Huber, Roland G, Bond, Peter J., and Warwicker, James

Subjects
Protein-protein interactions, protein specificity, lcsh:R, protein electrostatics, lcsh:Medicine, lcsh:Q, lcsh:Science, paralogue families
Abstract

An improved knowledge of protein-protein interactions is essential for better understanding of metabolic and signaling networks, and cellular function. Progress tends to be based on structure determination and predictions using known structures, along with computational methods based on evolutionary information or detailed atomistic descriptions. We hypothesized that for the case of interactions across a common interface, between proteins from a pair of paralogue families or within a family of paralogues, a relatively simple interface description could distinguish between binding and non-binding pairs. Using binding data for several systems, and large-scale comparative modeling based on known template complex structures, it is found that charge-charge interactions (for groups bearing net charge) are generally a better discriminant than buried non-polar surface. This is particularly the case for paralogue families that are less divergent, with more reliable comparative modeling. We suggest that electrostatic interactions are major determinants of specificity in such systems, an observation that could be used to predict binding partners.

Published
2017

148. Structure mapping of dengue and Zika viruses reveals new functional long-range interactions

Author

Huber, Roland G., primary, Lim, Xin Ni, additional, Ng, Wy Ching, additional, Sim, Adelene, additional, Poh, Hui Xian, additional, Shen, Yang, additional, Lim, Su Ying, additional, Sundstrom, Anna Karin Beatrice, additional, Sun, Xuyang, additional, Aw, Jong Ghut, additional, Too, Horng Khit, additional, Boey, Peng Hee, additional, Wilm, Andreas, additional, Chawla, Tanu, additional, Choy, Ming Ju, additional, Jiang, Lu, additional, de Sessions, Paola Florez, additional, Loh, Xian Jun, additional, Alonso, Sylvie, additional, Hibberd, Martin, additional, Nagarajan, Niranjan, additional, Ooi, Eng Eong, additional, Bond, Peter J., additional, Sessions, October M., additional, and Wan, Yue, additional

Published
2018
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