LAUSR

Significance Stress granules (SGs) are membraneless organelles regulating many vital biochemical processes. G3BP1 plays a critical role in regulating SG dynamics through its interaction with Caprin-1 and USP10. The crystal structures of the NTF2L domain of G3BP1 in complex with the G3BP1-interacting motif (GIM) of Caprin-1 and USP10 showed that both GIMs interact with the same pocket of G3BP1. Both GIMs suppressed the liquid–liquid phase separation (LLPS) of G3BP1, suggesting that Caprin-1 facilitates SG formation via other mechanisms. The C-terminal domain underwent spontaneous LLPS and promoted SG formation, whereas the N-terminal domain and GIM of Caprin-1 suppressed LLPS and SG formation. We propose that Caprin-1 regulates SG dynamics by a “yin and yang” mechanism of its N- and C-terminal domains.