{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T19:44:52Z","timestamp":1792439092170,"version":"4.5.0"},"reference-count":36,"publisher":"National Academy of Sciences","issue":"46","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2005,11,15]]},"abstract":"<jats:p>Wiskott\u2013Aldrich syndrome protein (WASP)-homology domain 2 (WH2) is a small and widespread actin-binding motif. In the WASP family, WH2 plays a role in filament nucleation by Arp2\/3 complex. Here we describe the crystal structures of complexes of actin with the WH2 domains of WASP, WASP-family verprolin homologous protein, and WASP-interacting protein. Despite low sequence identity, WH2 shares structural similarity with the N-terminal portion of the actin monomer-sequestering thymosin \u03b2 domain (T\u03b2). We show that both domains inhibit nucleotide exchange by targeting the cleft between actin subdomains 1 and 3, a common binding site for many unrelated actin-binding proteins. Importantly, WH2 is significantly shorter than T\u03b2 but binds actin with \u224810-fold higher affinity. WH2 lacks a C-terminal extension that in T\u03b24 becomes involved in monomer sequestration by interfering with intersubunit contacts in F-actin. Owing to their shorter length, WH2 domains connected in tandem by short linkers can coexist with intersubunit contacts in F-actin and are proposed to function in filament nucleation by lining up actin subunits along a filament strand. The WH2-central region of WASP-family proteins is proposed to function in an analogous way by forming a special class of tandem repeats whose function is to line up actin and Arp2 during Arp2\/3 nucleation. The structures also suggest a mechanism for how profilin-binding Pro-rich sequences positioned N-terminal to WH2 could feed actin monomers directly to WH2, thereby playing a role in filament elongation.<\/jats:p>","DOI":"10.1073\/pnas.0507021102","type":"journal-article","created":{"date-parts":[[2005,11,7]],"date-time":"2005-11-07T20:33:47Z","timestamp":1131395627000},"page":"16644-16649","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":265,"title":["Actin-bound structures of Wiskott\u2013Aldrich syndrome protein (WASP)-homology domain 2 and the implications for filament assembly"],"prefix":"10.1073","volume":"102","author":[{"given":"David","family":"Chereau","sequence":"first","affiliation":[{"name":"Boston Biomedical Research Institute, 64 Grove Street, Watertown, MA 02472"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic","family":"Kerff","sequence":"additional","affiliation":[{"name":"Boston Biomedical 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