2a41 | pdb_00002a41
Ternary complex of the WH2 Domain of WIP with Actin-DNAse I
Structural highlights
Disease[WIPF1_HUMAN] Defects in WIPF1 are the cause of Wiskott-Aldrich syndrome type 2 (WAS2) [MIM:614493]. WAS2 is an immunodeficiency disorder characterized by eczema, thrombocytopenia, recurrent infections, defective T-cell proliferation, and impaired natural killer cell function.[1] Function[ACTS_RABIT] Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. [WIPF1_HUMAN] May have direct activity on the actin cytoskeleton. Induces actin polymerization and redistribution. Contributes with NCK1 and GRB2 in the recruitment and activation of WASL. May participate in regulating the subcellular localization of WASL, resulting in the disassembly of stress fibers in favor of filopodia formation (By similarity). Plays an important role in the intracellular motility of vaccinia virus by functioning as an adapter for recruiting WASL to vaccinia virus.[2] [3] [DNAS1_BOVIN] Among other functions, seems to be involved in cell death by apoptosis. Binds specifically to G-actin and blocks actin polymerization (By similarity). 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 protein (WASP)-homology domain 2 (WH2) is a small and widespread actin-binding motif. In the WASP family, WH2 plays a role in filament nucleation by Arp2/3 complex. Here we describe the crystal structures of complexes of actin with the WH2 domains of WASP, WASP-family verprolin homologous protein, and WASP-interacting protein. Despite low sequence identity, WH2 shares structural similarity with the N-terminal portion of the actin monomer-sequestering thymosin beta domain (Tbeta). We show that both domains inhibit nucleotide exchange by targeting the cleft between actin subdomains 1 and 3, a common binding site for many unrelated actin-binding proteins. Importantly, WH2 is significantly shorter than Tbeta but binds actin with approximately 10-fold higher affinity. WH2 lacks a C-terminal extension that in Tbeta4 becomes involved in monomer sequestration by interfering with intersubunit contacts in F-actin. Owing to their shorter length, WH2 domains connected in tandem by short linkers can coexist with intersubunit contacts in F-actin and are proposed to function in filament nucleation by lining up actin subunits along a filament strand. The WH2-central region of WASP-family proteins is proposed to function in an analogous way by forming a special class of tandem repeats whose function is to line up actin and Arp2 during Arp2/3 nucleation. The structures also suggest a mechanism for how profilin-binding Pro-rich sequences positioned N-terminal to WH2 could feed actin monomers directly to WH2, thereby playing a role in filament elongation. Actin-bound structures of Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 and the implications for filament assembly.,Chereau D, Kerff F, Graceffa P, Grabarek Z, Langsetmo K, Dominguez R Proc Natl Acad Sci U S A. 2005 Nov 15;102(46):16644-9. Epub 2005 Nov 7. PMID:16275905[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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