文献类型：期刊文献

英文题名：Insights into the client protein release mechanism of the ATP-independent chaperone Spy

作者：He, Wei[1];Li, Xinming[2];Xue, Hongjuan[3];Yang, Yuanyuan[1];Mencius, Jun[1];Bai, Ling[1];Zhang, Jiayin[1];Xu, Jianhe[1];Wu, Bin[3];Xue, Yi[2];Quan, Shu[1,4]

机构：[1]East China Univ Sci & Technol, Shanghai Collaborat Innovat Ctr Biomfg SCICB, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Tsinghua Univ, Tsinghua Peking Joint Ctr Life Sci, Beijing Adv Innovat Ctr Struct Biol, Sch Life Sci, Beijing 100084, Peoples R China;[3]Chinese Acad Sci, Shanghai Adv Res Inst, ZhangJiang Lab, Natl Facil Prot Sci Shanghai, Shanghai 201210, Peoples R China;[4]East China Univ Sci & Technol, Shanghai Frontiers Sci Ctr Optogenet Tech Cell Me, Shanghai 200237, Peoples R China

年份：2022

卷号：13

期号：1

外文期刊名：NATURE COMMUNICATIONS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000799632400019)】；

基金：We thank James C. A. Bardwell (University of Michigan) and Bikash Ranjan Sahoo (University of Michigan) for helpful suggestions and insightful discussion. We thank Dr. Ning Xu in the BioNMR facility of the China National Center for Protein Sciences Beijing, for providing facility assistance. This work was supported by the National Natural Science Foundation of China (NSFC) grants 31661143021 and 31400664 (to S.Q.), funds from the Tsinghua-Peking Joint Center for Life Sciences and Beijing Advanced Innovation Center for Structural Biology (to Y.X.), the Fundamental Research Funds for the Central Universities (22221818014 to J.X.), the Research Program of State Key Laboratory of Bioreactor Engineering (to S.Q.), and the Shanghai Frontier Science Center of Optogenetic Techniques for Cell Metabolism Shanghai Municipal Education Commission, grant 2021 Sci & Tech 03 28 (to S.Q.).

语种：英文

摘要：How ATP-independent chaperones release their clients without energy input remains enigmatic. Here the authors discover that chaperone Spy uses its long, disordered N terminus to facilitate client release through competitive, dynamic intramolecular interactions with Spy's client binding surface. Molecular chaperones play a central role in regulating protein homeostasis, and their active forms often contain intrinsically disordered regions (IDRs). However, how IDRs impact chaperone action remains poorly understood. Here, we discover that the disordered N terminus of the prototype chaperone Spy facilitates client release. With NMR spectroscopy and molecular dynamics simulations, we find that the N terminus can bind transiently to the client-binding cavity of Spy primarily through electrostatic interactions mediated by the N-terminal D26 residue. This intramolecular interaction results in a dynamic competition of the N terminus with the client for binding to Spy, which promotes client discharge. Our results reveal the mechanism by which Spy releases clients independent of energy input, thus enriching the current knowledge on how ATP-independent chaperones release their clients and highlighting the importance of synergy between IDRs and structural domains in regulating protein function.