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Protein-protein interaction regulates proteins’ mechanical stability

TitleProtein-protein interaction regulates proteins’ mechanical stability
Publication TypeJournal Article
Year of Publication2008
AuthorsCao, Y, Yoo, T, Zhuang, SL, Li, HB
JournalJournal of Molecular Biology
Volume378
Pagination1132-1141
Date PublishedMay
Type of ArticleArticle
ISBN Number0022-2836
KeywordsBINDING, BIOLOGICAL ROLES, CRYSTAL-STRUCTURE, DIHYDROFOLATE-REDUCTASE, DOMAIN, ENGINEERING PROTEINS, FORCE SPECTROSCOPY, FRAGMENT, HUMAN-IGG, MECHANICAL STABILITY, mechanical unfolding, MOLECULAR ELASTICITY, protein-protein interaction, single molecule atomic force microscopy, STABILIZATION
Abstract

Elastomeric proteins are molecular springs found not only in a variety of biological machines and tissues, but also in biomaterials of superb mechanical properties. Regulating the mechanical stability of elastomeric proteins is not only important for a range of biological processes, but also critical for the use of engineered elastomeric proteins as building blocks to construct nanomechanical devices and novel materials of well-defined mechanical properties. Here we demonstrate that protein-protein interactions can potentially serve as an effective means to regulate the mechanical properties of elastomeric proteins. We show that the binding of fragments of IgG antibody to a small protein, GB1, can significantly enhance the mechanical stability of GB1. The regulation of the mechanical stability of GB1 by IgG fragments is not through direct modification of the interactions in the mechanically key region of GB1; instead, it is accomplished via the long-range coupling between the IgG binding site and the mechanically key region of GB1. Although Fc and Fab bind GB1 at different regions of GB1, their binding to GB1 can increase the mechanical stability of GB1 significantly. Using alanine point mutants of GB1, we show that the amplitude of mechanical stability enhancement of GB1 by Fc does not correlate with the binding affinity, suggesting that binding affinity only affects the population of GB1/human Fc (hFc) complex at a given concentration of hFc, but does not affect the intrinsic mechanical stability of the GB1/hFc complex. Furthermore, our results indicate that the mechanical stability enhancement by IgG fragments is robust and can tolerate sequence/structural perturbation to GB1. Our results demonstrate that the protein-protein interaction is an efficient approach to regulate the mechanical stability of GB1-like proteins and we anticipate that this new methodology will help to develop novel elastomeric proteins with tunable mechanical stability and compliance. (C) 2008 Elsevier Ltd. All rights reserved.

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