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 and Bruce L. Goode
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 beta-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. (C) 2016 The Authors. Published by Elsevier Ltd.
Structural Basis of Arp2/3 Complex Inhibition by GMF, Coronin, and Arpin
Creators
Olga S. Sokolova - Lomonosov Moscow State University
Angelina Chemeris - École Polytechnique
Siyang Guo - Brandeis University
Salvatore L. Alioto - Brandeis University
Meghal Gandhi - Brandeis University
Shae Padrick - Drexel University
Evgeniya Pechnikova - A.V. Shubnikov Institute of Crystallography
Violaine David - École Polytechnique
Alexis Gautreau - École Polytechnique
Bruce L. Goode - Brandeis University
Publication Details
Journal of molecular biology, v 429(2)
Publisher
Elsevier
Number of pages
12
Grant note
HHMI; Howard Hughes Medical Institute
17-14-00043 / Russian Science Foundation; Russian Science Foundation (RSF)
14-14-00234 / Russian Science Foundation; Russian Science Foundation (RSF)
I-1544 / Welch Foundation; The Welch Foundation
R01GM056322 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS)
R01-GM56322; GM063691 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
Resource Type
Journal article
Language
English
Academic Unit
Biochemistry and Molecular Biology
Web of Science ID
WOS:000393542200005
Scopus ID
2-s2.0-85008230376
Other Identifier
991019167984804721
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