文献类型：期刊文献

英文题名：Molecular Characterization of an Intrinsically Disordered Chaperone Reveals Net-Charge Regulation in Chaperone Action

作者：Ren, Chang[1];Zheng, Yongxin[1];Liu, Chunlan[1];Mencius, Jun[1];Wu, Zhili[1];Quan, Shu[1,2]

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]Shanghai Frontiers Sci Ctr Optogenet Tech Cell Me, Shanghai 200237, Peoples R China

年份：2022

卷号：434

期号：5

外文期刊名：JOURNAL OF MOLECULAR BIOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000788241300011)】；

基金：Acknowledgments We thank Cuiting Yang for the assistance in the initial stages of this study. We acknowledge all members of our laboratory for their technical support and helpful recommendations. This work was supported by National Natural Science Foundation of China (NSFC) grants 32171269 and 31661143021 (to S.Q.) , the Fundamental Research Funds for the Central Universities (22221818014 to S.Q.) , the Research Program of State Key Laboratory of Bioreactor Engineering (to S.Q.) , and a grant from Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism (Shanghai Municipal Education Commission, grant 2021 Sci & Tech 03-28) .

语种：英文

外文关键词：chaperone; intrinsically disordered protein; net-charge regulation; protein aggregation; stress response

摘要：Molecular chaperones are diverse biomacromolecules involved in the maintenance of cellular protein homeostasis (proteostasis). Here we demonstrate that in contrast to most chaperones with defined three-dimensional structures, the acid-inducible protein Asr in Escherichia coli is intrinsically disordered and exhibits varied aggregation-preventing or aggregation-promoting activities, acting as a "conditionally active chaperone". Bioinformatics and experimental analyses of Asr showed that it is devoid of hydrophobic patches but rich in positive charges and local polyproline II backbone structures. Asr contributes to the integrity of the bacterial outer membrane under mildly acidic conditions in vivo and possesses chaperone activities toward model clients in vitro. Notably, its chaperone activity is dependent on the net charges of clients: on the one hand, it inhibits the aggregation of clients with similar net charges; on the other hand, it stimulates the aggregation of clients with opposite net charges. Mutational analysis confirmed that positively charged residues in Asr are essential for the varied effects on protein aggregation, suggesting that electrostatic interactions are the major driving forces underlying Asr's proteostasis-related activity. These findings present a unique example of an intrinsically disordered molecular chaperone with distinctive dual functions-as an aggregase or as a chaperone-depending on the net charges of clients.(c) 2021 Elsevier Ltd. All rights reserved.