Multivalent lipid targeting by the calcium-independent C2A domain of synaptotagmin-like protein 4/granuphilin.

ABSTRACT: Synaptotagmin-like protein 4 (Slp-4), also known as granuphilin, is a Rab effector responsible for docking secretory vesicles to the plasma membrane before exocytosis. Slp-4 binds vesicular Rab proteins via an N-terminal Slp homology domain, interacts with plasma membrane SNARE complex proteins via a central linker region, and contains tandem C-terminal C2 domains (C2A and C2B) with affinity for phosphatidylinositol-(4,5)-bisphosphate (PIP₂). The Slp-4 C2A domain binds with low nanomolar apparent affinity to PIP₂ in lipid vesicles that also contain background anionic lipids such as phosphatidylserine but much weaker when either the background anionic lipids or PIP₂ is removed. Through computational and experimental approaches, we show that this high-affinit

SUBMITTER: Alnaas AA 

PROVIDER: S-EPMC7857503 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature