2a41
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Ternary complex of the WH2 Domain of WIP with Actin-DNAse I
OverviewOverview
Wiskott-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.
DiseaseDisease
Known disease associated with this structure: Breast cancer OMIM:[605100]
About this StructureAbout this Structure
2A41 is a Protein complex structure of sequences from Bos taurus and Oryctolagus cuniculus with CA, MG, ATP and FMT as ligands. Active as Deoxyribonuclease I, with EC number 3.1.21.1 Full crystallographic information is available from OCA.
ReferenceReference
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
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