Conformational changes in the Arp2/3 complex leading to actin nucleation

Nat Struct Mol Biol. 2005 Jan;12(1):26-31. doi: 10.1038/nsmb870. Epub 2004 Dec 12.


The two actin-related subunits of the Arp2/3 complex, Arp2 and Arp3, are proposed to form a pseudo actin dimer that nucleates actin polymerization. However, in the crystal structure of the inactive complex, they are too far apart to form such a nucleus. Here, we show using EM that yeast and bovine Arp2/3 complexes exist in a distribution among open, intermediate and closed conformations. The crystal structure docks well into the open conformation. The activator WASp binds at the cleft between Arp2 and Arp3, and all WASp-bound complexes are closed. The inhibitor coronin binds near the p35 subunit, and all coronin-bound complexes are open. Activating and loss-of-function mutations in the p35 subunit skew conformational distribution in opposite directions, closed and open, respectively. We conclude that WASp stabilizes p35-dependent closure of the complex, holding Arp2 and Arp3 closer together to nucleate an actin filament.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actin-Related Protein 2
  • Actin-Related Protein 3
  • Actins / chemistry*
  • Actins / metabolism*
  • Animals
  • Cattle
  • Crystallography, X-Ray
  • Cytoskeletal Proteins / chemistry*
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Cytoskeletal Proteins / ultrastructure
  • Microfilament Proteins / chemistry
  • Microfilament Proteins / metabolism
  • Microscopy, Electron
  • Protein Binding
  • Protein Conformation
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • Saccharomyces cerevisiae / chemistry
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism
  • Wiskott-Aldrich Syndrome Protein


  • Actin-Related Protein 2
  • Actin-Related Protein 3
  • Actins
  • Cytoskeletal Proteins
  • LAS17 protein, S cerevisiae
  • Microfilament Proteins
  • Protein Subunits
  • Saccharomyces cerevisiae Proteins
  • Wiskott-Aldrich Syndrome Protein
  • coronin proteins