1t44

From Proteopedia

Structural basis of actin sequestration by thymosin-B4: Implications for arp2/3 activation

Overview

The WH2 (Wiscott-Aldridge syndrome protein homology domain 2) repeat is an actin interacting motif found in monomer sequestering and filament assembly proteins. We have stabilized the prototypical WH2 family member, thymosin-beta4 (Tbeta4), with respect to actin, by creating a hybrid between gelsolin domain 1 and the C-terminal half of Tbeta4 (G1-Tbeta4). This hybrid protein sequesters actin monomers, severs actin filaments and acts as a leaky barbed end cap. Here, we present the structure of the G1-Tbeta4:actin complex at 2 A resolution. The structure reveals that Tbeta4 sequesters by capping both ends of the actin monomer, and that exchange of actin between Tbeta4 and profilin is mediated by a minor overlap in binding sites. The structure implies that multiple WH2 motif-containing proteins will associate longitudinally with actin filaments. Finally, we discuss the role of the WH2 motif in arp2/3 activation.

Disease

Known diseases associated with this structure: Myopathy, actin, congenital, with cores OMIM:[102610], Myopathy, actin, congenital, with excess of thin myofilaments OMIM:[102610], Myopathy, congenital, with fiber-type disporportion 1 OMIM:[102610], Myopathy, nemaline, 3 OMIM:[102610]

About this Structure

1T44 is a Protein complex structure of sequences from Homo sapiens, mus musculus and Oryctolagus cuniculus with and as ligands. Full crystallographic information is available from OCA.

Reference

Structural basis of actin sequestration by thymosin-beta4: implications for WH2 proteins., Irobi E, Aguda AH, Larsson M, Guerin C, Yin HL, Burtnick LD, Blanchoin L, Robinson RC, EMBO J. 2004 Sep 15;23(18):3599-608. Epub 2004 Aug 26. PMID:15329672

Page seeded by OCA on Thu Feb 21 15:09:43 2008