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

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

Author information

1
Department of Biology, Moscow M.V. Lomonosov University, Moscow 119234, Russia.
2
Department of Biology, Moscow M.V. Lomonosov University, Moscow 119234, Russia; Ecole Polytechnique, CNRS UMR7654, Palaiseau 91120, France.
3
Department of Biology, Brandeis University, Waltham, MA 02453, USA.
4
Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA 19102, USA.
5
V.A. Shoubnikov Institute of Crystallography RAS, Moscow 119333, Russia.
6
Ecole Polytechnique, CNRS UMR7654, Palaiseau 91120, France.
7
Department of Biology, Brandeis University, Waltham, MA 02453, USA. Electronic address: goode@brandeis.edu.

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.

KEYWORDS:

actin nucleation; conformation; single-particle EM; yeast

PMID:
27939292
PMCID:
PMC5350076
DOI:
10.1016/j.jmb.2016.11.030
[Indexed for MEDLINE]
Free PMC Article

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