7XHF

Crystal structure of the NTF2L domain of human G3BP1 in complex with the USP10 derived peptide

Summary for 7XHF

• Entry DOI: 10.2210/pdb7xhf/pdb
• Descriptor: Ras GTPase-activating protein-binding protein 1, USP10/6-21 (2 entities in total)
• Functional Keywords: complex, stress granules, lipid-lipid phase separation, rna binding protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 35700.25

Authors

Dan, S.,Weimin, G. (deposition date: 2022-04-08, release date: 2023-01-18, Last modification date: 2023-11-29)

Primary citation

Song, D.,Kuang, L.,Yang, L.,Wang, L.,Li, H.,Li, X.,Zhu, Z.,Shi, C.,Zhu, H.,Gong, W.
Yin and yang regulation of stress granules by Caprin-1.
Proc.Natl.Acad.Sci.USA, 119:e2207975119-e2207975119, 2022

PubMed Abstract: 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.

PubMed: 36279435
DOI: 10.1073/pnas.2207975119

Experimental method

X-RAY DIFFRACTION (2.68 Å)