2vcp | pdb_00002vcp
Crystal structure of N-Wasp VC domain in complex with skeletal actin
Structural highlights
FunctionACTS_RABIT Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedWiskott-Aldrich Syndrome Proteins (WASP) are a family of proteins that all catalyze actin filament branching with Arp2/3 complex in a variety of actin-based motile processes. The constitutively active C-terminal domain, called VCA, harbors one or more WASP Homology 2 (WH2) domains that bind G-actin, while the CA extension binds Arp2/3 complex. The VCA-actin-Arp2/3 entity associates with a mother filament to form a branched junction from which a daughter filament is initiated. The number and function of WH2-bound actin(s) in the branching process is not known, and the stoichiometry of VCA-actin-Arp2/3 complex is debated. We have expressed the tandem WH2 repeats of N-WASP, either alone (V) or associated with the C (VC) and CA (VCA) extensions. We analyze the structure of actin in complex with V, VC and VCA using protein crystallography, hydrodynamic and spectrofluorimetric methods. The partial crystal structure of VC :actin 1 :1 complex shows two actins in the asymmetric unit with extensive actin-actin contacts. In solution, each of the 2 WH2 domains in V, VC and VCA binds G-actin in 1 :2 complexes that participate in barbed end assembly. V, VC and VCA enhance barbed end depolymerization like profilin, but neither nucleate nor sever filaments, in contrast with other WH2 repeats. VCA binds Arp2/3 complex in a 1 :1 complex even in the presence of a large excess of VCA. VCA-Arp2/3 binds one actin in a Latrunculin A-sensitive fashion, in a 1 :1 :1 complex, indicating that binding of the second actin to VCA is weakened in the ternary complex. Interactions of isolated C-terminal fragments of Neural Wiskott-Aldrich Syndrome Protein (N-WASP) with actin and Arp2/3 complex.,Gaucher JF, Mauge C, Didry D, Guichard B, Renault L, Carlier MF J Biol Chem. 2012 Jul 30. PMID:22847007[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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