New mechanistic insights into the RAS-SIN1 interaction at the membrane.

ABSTRACT: Stress-activated MAP kinase-interacting protein 1 (SIN1) is a central member of the mTORC2 complex that contains an N-terminal domain (NTD), a conserved region in the middle (CRIM), a RAS-binding domain (RBD), and a pleckstrin homology domain. Recent studies provided valuable structural and functional insights into the interactions of SIN1 and the RAS-binding domain of RAS proteins. However, the mechanism for a reciprocal interaction of the RBD-PH tandem with RAS proteins and the membrane as an upstream event to spatiotemporal mTORC2 regulation is not clear. The biochemical assays in this study led to the following results: 1) all classical RAS paralogs, including HRAS, KRAS4A, KRAS4B, and NRAS, can bind to SIN1-RBD in biophysical and SIN1 full length (FL) in cell biology experiments; 2) t

SUBMITTER: Pudewell S 

PROVIDER: S-EPMC9583166 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature