Structural Basis of Arp2/3 Complex Inhibition by GMF, Coronin, and Arpin. Issue 2 (20th January 2017)

• Record Type: Journal Article
• Authors: Sokolova, Olga S.; Chemeris, Angelina; Guo, Siyang; Alioto, Salvatore L.; Gandhi, Meghal; Padrick, Shae; Pechnikova, Evgeniya; David, Violaine; Gautreau, Alexis; Goode, Bruce L.
• Is Part Of: Journal of molecular biology. Volume 429:Issue 2(2017)
• Page Start: 237
• Page End: 248
• Publication Date: 2017-01-20
• Subjects: Arp actin-related protein -- NPF nucleation-promoting factor -- GFP green fluorescent protein -- GMF glia maturation factor -- EM electron microscopy -- GST glutathione S-transferase -- FSC Fourier shell correlation -- TEV tobacco etch virus -- VCA verproline central acidic -- WASP Wiskott Aldrich syndrome protein -- WAVE WASP family verproline-homologous; actin nucleation -- single-particle EM -- yeast -- conformation; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2016.11.030
• Languages: English
• ISSNs: 0022-2836

Abstract

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. Graphical Abstract: Highlights: Coronin, GMF, and Arpin each induce related open conformations in Arp2/3 complex. GMF binding induces two distinct inhibitory states of Arp2/3 complex. Coronin, GMF, and Arpin combinatorially inhibit Arp2/3 complex activity. Arpin has two separate binding sites on Arp2/3 complex Arp2 and Arp3.