Hsp40 proteins phase separate to chaperone the assembly and maintenance of membraneless organelles
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- Jinge Gu
- Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China;
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- Zhenying Liu
- Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China;
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- Shengnan Zhang
- Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China;
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- Yichen Li
- Bio-X-Renji Hospital Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, China;
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- Wencheng Xia
- Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China;
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- Chen Wang
- Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China;
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- Huaijiang Xiang
- Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China;
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- Zhijun Liu
- National Facility for Protein Science in Shanghai, Zhangjiang Laboratory, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210, China;
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- Li Tan
- Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China;
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- Yanshan Fang
- Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China;
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- Cong Liu
- Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China;
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- Dan Li
- Bio-X-Renji Hospital Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, China;
抄録
<jats:title>Significance</jats:title> <jats:p>Protein phase separation is a progressive process of high-ordered assembly in vitro, which can experience dynamic liquid–liquid phase separation (LLPS) followed by maturation into pathological solid fibrils. The latter is closely associated with neurodegenerative disorders, such as amyotrophic lateral sclerosis and frontotemporal dementia. In cells, protein phase separation is tightly regulated to maintain a metastable state of molecular condensates and avoid further aberrant aggregation. However, this regulation process is largely unknown. Our paper demonstrates that Hsp40 (DNAJ) proteins, e.g., Hdj1 (DNAJB1) and Hdj2 (DNAJA1), have a strong ability of LLPS, which enables Hsp40 to incorporate into stress granules, and stabilize the amyloid-forming proteins, e.g., FUS, in the condensed phase-separated state rather than proceeding to toxic aggregation.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 117 (49), 31123-31133, 2020-11-23
Proceedings of the National Academy of Sciences