Molecular mechanism of Arp2/3 complex activation by nucleation-promoting factors and an actin monomer.

ABSTRACT: Arp (actin-related protein) 2/3 complex nucleates actin filament branches on the sides of preexisting actin filaments during cell and organelle movements. We used computer simulations of mammalian Arp2/3 complex to address fundamental questions about the mechanism. Metadynamics and umbrella free energy sampling simulations of the pathway revealed that a clash between the D-loop of Arp2 and Arp3 produces an energy barrier of 20 ± 6 kcal/mol between the inactive splayed and active short-pitch conformations of Arp2/3 complex. Atomistic molecular dynamics simulations showed that binding the CA motif of the nucleation-promoting factor Neuronal Wiskott-Aldrich Syndrome Protein (N-WASp) to inactive, splayed Arp2/3 complex shifts it toward the short-pitch active conformation and opens a binding si

SUBMITTER: Sridharan Iyer S 

PROVIDER: S-EPMC11912402 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature