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

Olga S. Sokolova, Angelina Chemeris, Siyang Guo, Salvatore L. Alioto, Meghal Gandhi, Shae Padrick, Evgeniya Pechnikova, Violaine David, Alexis Gautreau, Bruce L. Goode

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)237-248
Number of pages12
JournalJournal of Molecular Biology
Volume429
Issue number2
DOIs
StatePublished - Jan 20 2017

Keywords

  • actin nucleation
  • conformation
  • single-particle EM
  • yeast

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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    Sokolova, O. S., Chemeris, A., Guo, S., Alioto, S. L., Gandhi, M., Padrick, S., Pechnikova, E., David, V., Gautreau, A., & Goode, B. L. (2017). Structural Basis of Arp2/3 Complex Inhibition by GMF, Coronin, and Arpin. Journal of Molecular Biology, 429(2), 237-248. https://doi.org/10.1016/j.jmb.2016.11.030