Targeting G3BP1 Condensate Topology Promotes Stress Granule Assembly via m⁶A-IGF2BP1 for Ischemic Stroke Rescue.

ABSTRACT: Ras-GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) mediates stress granules (SGs) via phase separation. However, there is limited understanding of the allosteric mechanism and the identification of regulatory molecules. Here, we identify icariin (ICA), a small-molecule inducer that promotes G3BP1-driven biomolecular condensate formation, which effectively restructures SGs architecture. Moreover, we demonstrate that ICA interacts with the N-terminal nuclear transport factor 2-like (NTF2L) domain of G3BP1, inducing a conformational switch from "closed-to-open" that facilitates G3BP1 oligomerization and phase separation. Crucially, G3BP1 condensates recruit N⁶-methyladenosine (m⁶A) reader insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) throu

SUBMITTER: Li L 

PROVIDER: S-EPMC12866838 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature