文章基本信息

标题：Hsp70 exhibits a liquid-liquid phase separation ability and chaperones condensed FUS against amyloid aggregation
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作者：Yichen Li ; Jinge Gu ; Chen Wang 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：6
页码：1-16
DOI：10.1016/j.isci.2022.104356
语种：English
出版社：Elsevier
摘要：SummaryHsp70 is a key molecular chaperone in the protein quality control system to safeguard protein homeostasis in cells. Previous studies have shown that Hsp70 chaperones TDP-43, a pathogenic protein associated with amyotrophic lateral sclerosis (ALS), in nuclear bodies and prevents it from the pathological aggregation. In this work, we report that Hsp70 undergoes liquid-liquid phase separation, chaperones FUS, another ALS-linked pathogenic protein, in stress granules (SGs), and prevents condensed FUS from amyloid aggregation. Knock-down of Hsp70 does not influence SG assembly but results in the liquid-to-solid transition in SGs. NMR experiments further reveal Hsp70 predominantly uses its C-terminal substrate-binding domain to interact with the low complexity domain of FUS, which represents a mechanism distinct from that interacting with TDP-43. These findings suggest that Hsp70 is widely involved in chaperoning the physiological dynamics of various membrane-less organelles and adopts different mechanisms to prevent the pathological aggregation of different proteins.Graphical abstractDisplay OmittedHighlights•Hsp70 features a high ability of liquid-liquid phase separationin vitro•Hsp70 modifies liquid properties of SGs•Hsp70 inhibits the liquid-to-solid phase transition of FUS•Hsp70-CTD predominantly binds FUS-LCCell biology; Organizational aspects of cell biology; Biophysics; Biophysical Chemistry