Rabphilin 3A binds the N-peptide of SNAP-25 to promote SNARE complex assembly in exocytosis.

ABSTRACT: Exocytosis of secretory vesicles requires the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins and small GTPase Rabs. As a Rab3/Rab27 effector protein on secretory vesicles, Rabphilin 3A was implicated to interact with SNAP-25 to regulate vesicle exocytosis in neurons and neuroendocrine cells, yet the underlying mechanism remains unclear. In this study, we have characterized the physiologically relevant binding sites between Rabphilin 3A and SNAP-25. We found that an intramolecular interplay between the N-terminal Rab-binding domain and C-terminal C₂AB domain enables Rabphilin 3A to strongly bind the SNAP-25 N-peptide region via its C₂B bottom α-helix. Disruption of this interaction significantly impaired docking and fusion of ves

SUBMITTER: Li T 

PROVIDER: S-EPMC9522249 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature