Structural basis of actin sequestration by thymosin β4: implications for WH2 proteins
2004 (English)In: EMBO Journal, ISSN 0261-4189, E-ISSN 1460-2075, Vol. 23, no 18, 3599-608 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2004. Vol. 23, no 18, 3599-608 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-94969DOI: 10.1038/sj.emboj.7600372PubMedID: 15329672OAI: oai:DiVA.org:uu-94969DiVA: diva2:169007