Structural Basis of Arp2/3 Complex Inhibition by GMF, Coronin, and Arpin

J Mol Biol. 2017 Jan 20;429(2):237-248. doi: 10.1016/j.jmb.2016.11.030. Epub 2016 Dec 6.


The evolutionarily conserved Arp2/3 complex plays a central role in nucleating the branched actin filament arrays that drive cell migration, endocytosis, and other processes. To better understand Arp2/3 complex regulation, we used single-particle electron microscopy to compare the structures of Arp2/3 complex bound to three different inhibitory ligands: glia maturation factor (GMF), Coronin, and Arpin. Although the three inhibitors have distinct binding sites on Arp2/3 complex, they each induced an "open" nucleation-inactive conformation. Coronin promoted a standard (previously described) open conformation of Arp2/3 complex, with the N-terminal β-propeller domain of Coronin positioned near the p35/ARPC2 subunit of Arp2/3 complex. GMF induced two distinct open conformations of Arp2/3 complex, which correlated with the two suggested binding sites for GMF. Furthermore, GMF synergized with Coronin in inhibiting actin nucleation by Arp2/3 complex. Arpin, which uses VCA-related acidic (A) motifs to interact with the Arp2/3 complex, induced the standard open conformation, and two new masses appeared at positions near Arp2 and Arp3. Furthermore, Arpin showed additive inhibitory effects on Arp2/3 complex with Coronin and GMF. Together, these data suggest that Arp2/3 complex conformation is highly polymorphic and that its activities can be controlled combinatorially by different inhibitory ligands.

Keywords: actin nucleation; conformation; single-particle EM; yeast.

Publication types

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

MeSH terms

  • 4-Butyrolactone / analogs & derivatives*
  • 4-Butyrolactone / pharmacology
  • Actin-Related Protein 2-3 Complex / antagonists & inhibitors
  • Actin-Related Protein 2-3 Complex / chemistry*
  • Binding Sites
  • Carrier Proteins / pharmacology*
  • Cell Movement / drug effects
  • Endocytosis / drug effects
  • Glia Maturation Factor / pharmacology*
  • Humans
  • Imaging, Three-Dimensional
  • Protein Conformation


  • Actin-Related Protein 2-3 Complex
  • Carrier Proteins
  • Glia Maturation Factor
  • arpin protein, human
  • coronin
  • 4-Butyrolactone