Structural basis for regulation of Arp2/3 complex by GMF

Nat Struct Mol Biol. 2013 Sep;20(9):1062-8. doi: 10.1038/nsmb.2628. Epub 2013 Jul 28.


The Arp2/3 complex mediates formation of complex cellular structures such as lamellipodia by nucleating branched actin filaments. Arp2/3-complex activity is precisely controlled by over a dozen regulators, yet the structural mechanism by which regulators interact with the complex is unknown. GMF is a recently discovered regulator of the Arp2/3 complex that can inhibit nucleation and disassemble branches. We solved the structure of the 240-kDa assembly of Mus musculus GMF and Bos taurus Arp2/3 complex and found that GMF binds the barbed end of Arp2, overlapping with the proposed binding site of WASP-family proteins. The structure suggests that GMF can bind branch junctions in the manner that cofilin binds filament sides, consistent with a modified cofilin-like mechanism for debranching by GMF. The GMF-Arp2 interface reveals how the ADF-H actin-binding domain in GMF is exploited to specifically recognize Arp2/3 complex and not actin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin-Related Protein 2-3 Complex / chemistry*
  • Actin-Related Protein 2-3 Complex / genetics
  • Actin-Related Protein 2-3 Complex / metabolism*
  • Actins / chemistry
  • Actins / metabolism
  • Amino Acid Sequence
  • Animals
  • Cattle
  • Crystallography, X-Ray
  • Glia Maturation Factor / chemistry*
  • Glia Maturation Factor / genetics
  • Glia Maturation Factor / metabolism*
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / metabolism
  • Protein Interaction Domains and Motifs
  • Protein Subunits
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Wiskott-Aldrich Syndrome Protein Family / chemistry
  • Wiskott-Aldrich Syndrome Protein Family / metabolism


  • Actin-Related Protein 2-3 Complex
  • Actins
  • Glia Maturation Factor
  • Multiprotein Complexes
  • Protein Subunits
  • Recombinant Proteins
  • Wiskott-Aldrich Syndrome Protein Family
  • glia maturation factor gamma

Associated data

  • PDB/4JD2