Structural basis of actin sequestration by thymosin-[beta]4: implications for WH2 proteins

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 gelsoli...

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Bibliographic Details
Published in:The EMBO journal 2004-09, Vol.23 (18), p.3599
Main Authors: Irobi, Edward, Aguda, Adeleke H, Larsson, Mårten, Guerin, Christophe, Yin, Helen L, Burtnick, Leslie D, Blanchoin, Laurent, Robinson, Robert C
Format: Article
Language:English
Subjects:
Proteins
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Summary: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.
ISSN:0261-4189
1460-2075
DOI:10.1038/sj.emboj.7600372