Hsp70 exhibits a liquid-liquid phase separation ability and chaperones condensed FUS against amyloid aggregation

iScience

Jiaojiao Hu¹  Yanshan Fang¹  Cong Liu¹  Jinge Gu²  Yichen Li³  Dan Li³  Shenqing Zhang⁴  Shengnan Zhang⁴  Chen Wang⁴ 

[1] University of the Chinese Academy of Sciences, Beijing 100049, China;Zhangjiang Institute for Advanced Study, Shanghai Jiao Tong University, Shanghai 200240, China;Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai 200030, China;Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China;

关键词: Cell biology;    Organizational aspects of cell biology;    Biophysics;    Biophysical chemistry;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: Hsp70 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.

【 授权许可】

Unknown