Analysis of the interactions between GMF and Arp2/3 complex in two binding sites by molecular dynamics simulation

Biochem Biophys Res Commun. 2018 Feb 5;496(2):529-535. doi: 10.1016/j.bbrc.2018.01.080. Epub 2018 Jan 12.

Abstract

The Arp2/3 complex plays a key role in nucleating actin filaments branching. The glia maturation factor (GMF) competes with activators for interacting with the Arp2/3 complex and initiates the debranching of actin filaments. In this study, we performed a comparative analysis of interactions between GMF and the Arp2/3 complex and identified new amino acid residues involved in GMF binding to the Arp2/3 complex at two separate sites, revealed by X-ray and single particle EM techniques. Using molecular dynamics simulations we demonstrated the quantitative and qualitative changes in hydrogen bonds upon binding with GMF. We identified the specific amino acid residues in GMF and Arp2/3 complex that stabilize the interactions and estimated the mean force profile for the GMF using umbrella sampling. Phylogenetic and structural analyses of the recently defined GMF binding site on the Arp3 subunit indicate a new mechanism for Arp2/3 complex inactivation that involves interactions between the Arp2/3 complex and GMF at two binding sites.

Keywords: Arp2/3 complex; Crystal structure; GMF; Inactivation; Molecular modeling; Single particle electron microscopy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin-Related Protein 2-3 Complex / chemistry
  • Actin-Related Protein 2-3 Complex / metabolism*
  • Animals
  • Binding Sites
  • Cattle
  • Crystallography, X-Ray
  • Glia Maturation Factor / chemistry
  • Glia Maturation Factor / metabolism*
  • Mice
  • Molecular Dynamics Simulation
  • Protein Binding
  • Protein Interaction Maps
  • Thermodynamics

Substances

  • Actin-Related Protein 2-3 Complex
  • Glia Maturation Factor