title: Structural basis for regulation of Arp2/3 complex by GMF.
abstract: The Arp2/3 complex mediates formation of complex cellular structures such as lamellipodia by nucleating branched actin filaments. Arp2/3-complex activity is precisely controlled by over a dozen regulators, yet the structural mechanism by which regulators interact with the complex is unknown. GMF is a recently discovered regulator of the Arp2/3 complex that can inhibit nucleation and disassemble branches. We solved the structure of the 240-kDa assembly of Mus musculus GMF and Bos taurus Arp2/3 complex and found that GMF binds the barbed end of Arp2, overlapping with the proposed binding site of WASP-family proteins. The structure suggests that GMF can bind branch junctions in the manner that cofilin binds filament sides, consistent with a modified cofilin-like mechanism for debranching by GMF. The GMF-Arp2 interface reveals how the ADF-H actin-binding domain in GMF is exploited to specifically recognize Arp2/3 complex and not actin.
authors.affiliation: 1] Institute of Molecular Biology, University of Oregon, Eugene, Oregon, USA. [2] Department of Chemistry and Biochemistry, University of Oregon, Eugene, Oregon, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Luan
authors.forename: Brad J
authors.initials: BJ
authors.lastname: Nolen
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000199:Actins / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D018360:Crystallography, X-Ray; D020904:Glia Maturation Factor / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D021122:Protein Subunits; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000737:chemistry / Q000378:metabolism
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D020904:Glia Maturation Factor; D046912:Multiprotein Complexes; D021122:Protein Subunits; D011994:Recombinant Proteins; D051300:Wiskott-Aldrich Syndrome Protein Family; C117487:glia maturation factor gamma
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