4jhd
From Proteopedia
Crystal Structure of an Actin Dimer in Complex with the Actin Nucleator Cordon-Bleu
Structural highlights
Function[ACT1_DROME] Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. Multiple isoforms are involved in various cellular functions such as cytoskeleton structure, cell mobility, chromosome movement and muscle contraction. [COBL_MOUSE] Plays an important role in the reorganization of the actin cytoskeleton. Binds to and sequesters actin monomers (G actin). Nucleates actin polymerization by assembling three actin monomers in cross-filament orientation and thereby promotes growth of actin filaments at the barbed end. Can also mediate actin depolymerization at barbed ends and severing of actin filaments. Promotes formation of cell ruffles. Regulates neuron morphogenesis and increases branching of axons and dendrites. Regulates dendrite branching in Purkinje cells.[1] [2] Publication Abstract from PubMedSpontaneous nucleation of actin is very inefficient in cells. To overcome this barrier, cells have evolved a set of actin filament nucleators to promote rapid nucleation and polymerization in response to specific stimuli. However, the molecular mechanism of actin nucleation remains poorly understood. This is hindered largely by the fact that actin nucleus, once formed, rapidly polymerizes into filament, thus making it impossible to capture stable multisubunit actin nucleus. Here, we report an effective double-mutant strategy to stabilize actin nucleus by preventing further polymerization. Employing this strategy, we solved the crystal structure of AMPPNP-actin in complex with the first two tandem W domains of Cordon-bleu (Cobl), a potent actin filament nucleator. Further sequence comparison and functional studies suggest that the nucleation mechanism of Cobl is probably shared by the p53 cofactor JMY, but not Spire. Moreover, the double-mutant strategy opens the way for atomic mechanistic study of actin nucleation and polymerization. Structural Basis of Actin Filament Nucleation by Tandem W Domains.,Chen X, Ni F, Tian X, Kondrashkina E, Wang Q, Ma J Cell Rep. 2013 May 29. pii: S2211-1247(13)00210-6. doi:, 10.1016/j.celrep.2013.04.028. PMID:23727244[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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