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- Dan Song
- School of Life Sciences, University of Science and Technology of China, Hefei, 230027 China
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- Lisha Kuang
- Department of Pharmacology and Toxicology, R. Ken Coit College of Pharmacy, University of Arizona, Tucson, AZ 85721
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- Lin Yang
- School of Life Sciences, University of Science and Technology of China, Hefei, 230027 China
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- Lei Wang
- Department of Pharmacology and Toxicology, R. Ken Coit College of Pharmacy, University of Arizona, Tucson, AZ 85721
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- Hao Li
- School of Life Sciences, University of Science and Technology of China, Hefei, 230027 China
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- Xiu Li
- School of Life Sciences, University of Science and Technology of China, Hefei, 230027 China
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- Zhimin Zhu
- Institute of Applied Physics, Chinese Academy of Sciences, 201899 Shanghai, China
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- Chaowei Shi
- School of Life Sciences, University of Science and Technology of China, Hefei, 230027 China
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- Haining Zhu
- Department of Pharmacology and Toxicology, R. Ken Coit College of Pharmacy, University of Arizona, Tucson, AZ 85721
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- Weimin Gong
- School of Life Sciences, University of Science and Technology of China, Hefei, 230027 China
抄録
<jats:p>Stress granules (SGs) are cytoplasmic biomolecular condensates containing proteins and RNAs in response to stress. Ras-GTPase–activating protein binding protein 1 (G3BP1) is a core SG protein. Caprin-1 and ubiquitin specific peptidase 10 (USP10) interact with G3BP1, facilitating and suppressing SG formation, respectively. The crystal structures of the nuclear transport factor 2-like (NTF2L) domain of G3BP1 in complex with the G3BP1-interacting motif (GIM) of Caprin-1 and USP10 show that both GIMs bind to the same hydrophobic pocket of G3BP1. Moreover, both GIMs suppressed the liquid–liquid phase separation (LLPS) of G3BP1, suggesting that Caprin-1 likely facilitates SG formation via other mechanisms. Thus, we dissected various domains of Caprin-1 and investigated their role in LLPS in vitro and SG formation in cells. The C-terminal domain of Caprin-1 underwent spontaneous LLPS, whereas the N-terminal domain and GIM of Caprin-1 suppressed LLPS of G3BP1. The opposing effect of the N- and C-terminal domains of Caprin-1 on SG formation were demonstrated in cells with or without the endogenous Caprin-1. We propose that the N- and C-terminal domains of Caprin-1 regulate SG formation in a “yin and yang” fashion, mediating the dynamic and reversible assembly of SGs.</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 119 (44), e2207975119-, 2022-10-24
Proceedings of the National Academy of Sciences