Engineering a membrane-binding protein to trimerize and induce high membrane curvature.

ABSTRACT: The annexins are a family of Ca²⁺-dependent peripheral membrane proteins. Several annexins are implicated in plasma membrane repair and are overexpressed in cancer cells. Annexin A4 (ANXA4) and annexin A5 (ANXA5) form trimers that induce high curvature on a membrane surface, a phenomenon deemed to accelerate membrane repair. Despite being highly homologous to ANXA4, annexin A3 (ANXA3) does not form trimers on the membrane surface. Using molecular dynamics simulations, we have reverse engineered an ANXA3-mutant to trimerize on the surface of the membrane and induce high curvature reminiscent of ANXA4. In addition, atomic force microscopy images show that, like ANXA4, the engineered protein forms crystalline arrays on a supported lipid membrane. Despite the trimer-forming and curv

SUBMITTER: Hakami Zanjani AA 

PROVIDER: S-EPMC10398344 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature