Different molecular recognition by three domains of the full-length GRB2 to SOS1 proline-rich motifs and EGFR phosphorylated sites.

ABSTRACT: The adaptor protein human GRB2 plays crucial roles in mediating signal transduction from cell membrane receptors to RAS and its downstream proteins by recruiting SOS1. Recent studies have revealed that GRB2 also serves as a scaffold for liquid-liquid phase separation (LLPS) with SOS1 and transmembrane receptors, which is thought to regulate the magnitude of cell signalling pathways. In this study, we employed solution NMR spectroscopy to investigate the interactions of the full-length GRB2 with proline-rich motifs (PRMs) derived from ten potential GRB2-binding sites in SOS1, as well as a peptide from a phosphorylation site of EGFR. Our findings indicate that the binding affinity of the two SH3 domains of GRB2 for PRMs differs by a factor of ten to twenty, with the N-terminal SH3 domain (NS

SUBMITTER: Tateno K 

PROVIDER: S-EPMC11391413 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature