Structural Basis of Actin Sequestration by Thymosin-beta4: Implications for WH2 Proteins

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2004 Aug 27

PMID 15329672

Citations 47

Authors

Edward Irobi

Adeleke H Aguda

Marten Larsson

Christophe Guerin

Helen L Yin

Leslie D Burtnick

Laurent Blanchoin

Robert C Robinson

Affiliations

Soon will be listed here.

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, 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.

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