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Crowded, cell-like environment induces shape changes in aspherical protein.

ABSTRACT: How the crowded environment inside cells affects the structures of proteins with aspherical shapes is a vital question because many proteins and protein-protein complexes in vivo adopt anisotropic shapes. Here we address this question by combining computational and experimental studies of a football-shaped protein (i.e., Borrelia burgdorferi VlsE) in crowded, cell-like conditions. The results show that macromolecular crowding affects protein-folding dynamics as well as overall protein shape. In crowded milieus, distinct conformational changes in VlsE are accompanied by secondary structure alterations that lead to exposure of a hidden antigenic region. Our work demonstrates the malleability of "native" proteins and implies that crowding-induced shape changes may be important for protein function and malfunction in vivo.

SUBMITTER: Homouz D

PROVIDER: S-EPMC2515223 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature

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Crowded, cell-like environment induces shape changes in aspherical protein.

Homouz Dirar D Perham Michael M Samiotakis Antonios A Cheung Margaret S MS Wittung-Stafshede Pernilla P

Proceedings of the National Academy of Sciences of the United States of America 20080812 33

How the crowded environment inside cells affects the structures of proteins with aspherical shapes is a vital question because many proteins and protein-protein complexes in vivo adopt anisotropic shapes. Here we address this question by combining computational and experimental studies of a football-shaped protein (i.e., Borrelia burgdorferi VlsE) in crowded, cell-like conditions. The results show that macromolecular crowding affects protein-folding dynamics as well as overall protein shape. In ...[more]

PMID: 18697933

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Project description:Large-scale analyses of protein-protein interactions based on coarse-grain molecular docking simulations and binding site predictions resulting from evolutionary sequence analysis, are possible and realizable on hundreds of proteins with variate structures and interfaces. We demonstrated this on the 168 proteins of the Mintseris Benchmark 2.0. On the one hand, we evaluated the quality of the interaction signal and the contribution of docking information compared to evolutionary information showing that the combination of the two improves partner identification. On the other hand, since protein interactions usually occur in crowded environments with several competing partners, we realized a thorough analysis of the interactions of proteins with true partners but also with non-partners to evaluate whether proteins in the environment, competing with the true partner, affect its identification. We found three populations of proteins: strongly competing, never competing, and interacting with different levels of strength. Populations and levels of strength are numerically characterized and provide a signature for the behavior of a protein in the crowded environment. We showed that partner identification, to some extent, does not depend on the competing partners present in the environment, that certain biochemical classes of proteins are intrinsically easier to analyze than others, and that small proteins are not more promiscuous than large ones. Our approach brings to light that the knowledge of the binding site can be used to reduce the high computational cost of docking simulations with no consequence in the quality of the results, demonstrating the possibility to apply coarse-grain docking to datasets made of thousands of proteins. Comparison with all available large-scale analyses aimed to partner predictions is realized. We release the complete decoys set issued by coarse-grain docking simulations of both true and false interacting partners, and their evolutionary sequence analysis leading to binding site predictions. Download site: http://www.lgm.upmc.fr/CCDMintseris/

Dataset Information

Crowded, cell-like environment induces shape changes in aspherical protein.

Publications

Crowded, cell-like environment induces shape changes in aspherical protein.

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