Structural basis of actin sequestration by thymosin-β4: Implications for WH2 proteins

Edward Irobi, Adeleke H. Aguda, Mårten Larsson, Christophe Guerin, Helen L. Yin, Leslie D. Burtnick, Laurent Blanchoin, Robert C. Robinson

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

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, thympsin-β4 (Tβ4), with respect to actin, by creating a hybrid between gelsolin domain 1 and the C-terminal half of Tβ4 (G1-Tβ4). 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-Tβ4:actin complex at 2 Å resolution. The structure reveals that Tβ4 sequesters by capping both ends of the actin monomer, and that exchange of actin between Tβ4 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.

Original languageEnglish
Pages (from-to)3599-3608
Number of pages10
JournalEMBO Journal
Volume23
Issue number18
DOIs
Publication statusPublished - Sep 15 2004
Externally publishedYes

Keywords

  • Protein crystallography
  • SCAR
  • VCA
  • WASp
  • WH2

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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  • Cite this

    Irobi, E., Aguda, A. H., Larsson, M., Guerin, C., Yin, H. L., Burtnick, L. D., Blanchoin, L., & Robinson, R. C. (2004). Structural basis of actin sequestration by thymosin-β4: Implications for WH2 proteins. EMBO Journal, 23(18), 3599-3608. https://doi.org/10.1038/sj.emboj.7600372