Protein Interaction Energy Landscapes are Shaped by Functional and also Non-functional Partners

JOURNAL OF MOLECULAR BIOLOGY

卷:432

Article

Schweke, Hugo¹  Mucchielli, Marie-Helene^1,2  Sacquin-Mora, Sophie^3,4  Bei, Wanying¹  Lopes, Anne¹ 

[1] Univ Paris Saclay, Univ Paris Sud, CNRS, Inst Integrat Biol Cell I2BC,CEA, 1 Ave Terrasse, F-91198 Gif Sur Yvette, France

[2] UPMC Univ Paris 06, Sorbonne Univ, UFR927, F-75005 Paris, France

[3] Univ Paris, CNRS, Lab Biochim Theor, UPR 9080, 13 Rue Pierre & Marie Curie, F-75005 Paris, France

[4] PSL Res Univ, Inst Biol Physicochim Fdn Edmond de Rothschild, Paris, France

关键词: protein docking;    protein interactions;    interaction energy landscapes;    non-functional interactions;    cross-docking;   

DOI  :  10.1016/j.jmb.2019.12.047

来源: Elsevier

【 摘 要 】

In the crowded cell, a strong selective pressure operates on the proteome to limit the competition between functional and non-functional protein-protein interactions. We developed an original theoretical framework in order to interrogate how this competition constrains the behavior of proteins with respect to their partners or random encounters. Our theoretical framework relies on a two-dimensional (2D) representation of interaction energy landscapes, with 2D energy maps, which reflect in a synthetic way the spatial distribution of the interaction propensity of a protein surface for another protein. We realized the interaction propensity mapping of proteins' surfaces in interaction with functional and arbitrary partners and asked whether the distribution of their interaction propensity is conserved during evolution. Therefore, we performed several thousands of cross-docking simulations to systematically characterize the energy landscapes of 103 proteins interacting with different sets of homologs, corresponding to their functional partner's family or arbitrary protein families. Then, we systematically compared the energy maps resulting from the docking of each protein with the different protein families of the dataset. Strikingly, we show that the interaction propensity not only of the binding sites but also of the rest of the surface is conserved for docking partners belonging to the same protein family. Interestingly, this observation holds for docked proteins corresponding to true but also arbitrary partners. Our theoretical framework enables the characterization of the energy behavior of a protein in interaction with hundreds of proteins and opens the way for the characterization of the behavior of proteins in a specific environment. (C) 2020 Published by Elsevier Ltd.

【 授权许可】

Free