Mechanism and cellular function of direct membrane binding by the ESCRT and ERES-associated Ca²⁺-sensor ALG-2.

ABSTRACT: Apoptosis Linked Gene-2 (ALG-2) is a multifunctional intracellular Ca²⁺ sensor and the archetypal member of the penta-EF hand protein family. ALG-2 functions in the repair of damage to both the plasma and lysosome membranes and in COPII-dependent budding at endoplasmic reticulum exit sites (ERES). In the presence of Ca²⁺, ALG-2 binds to ESCRT-I and ALIX in membrane repair and to SEC31A at ERES. ALG-2 also binds directly to acidic membranes in the presence of Ca²⁺ by a combination of electrostatic and hydrophobic interactions. By combining GUV-based experiments and molecular dynamics simulations, we show that charge-reversed mutants of ALG-2 at these locations disrupt membrane recruitment. ALG-2 membrane binding mutants have reduced or abrogated ERES localiz

SUBMITTER: Shukla S 

PROVIDER: S-EPMC10614929 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature