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A CapG gain-of-function mutant reveals critical structural and functional determinants for actin filament severing.
Zhang, Y; Vorobiev, Sergey M; Gibson, Bruce G; Hao, Binghua; Sidhu, Gurjit S; Mishra, Vishnu S; Yarmola, Elena G; Bubb, Michael R; Almo, Steven C; Southwick, Frederick S.
Afiliação
  • Zhang Y; Department of Medicine, University of Florida, Gainesville, 32610, USA.
EMBO J ; 25(19): 4458-67, 2006 Oct 04.
Article em En | MEDLINE | ID: mdl-16977317
CapG is the only member of the gelsolin family unable to sever actin filaments. Changing amino acids 84-91 (severing domain) and 124-137 (WH2-containing segment) simultaneously to the sequences of gelsolin results in a mutant, CapG-sev, capable of severing actin filaments. The gain of severing function does not alter actin filament capping, but is accompanied by a higher affinity for monomeric actin, and the capacity to bind and sequester two actin monomers. Analysis of CapG-sev crystal structure suggests a more loosely folded inactive conformation than gelsolin, with a shorter S1-S2 latch. Calcium binding to S1 opens this latch and S1 becomes separated from a closely interfaced S2-S3 complex by an extended arm consisting of amino acids 118-137. Modeling with F-actin predicts that the length of this WH2-containing arm is critical for severing function, and the addition of a single amino acid (alanine or histidine) eliminates CapG-sev severing activity, confirming this prediction. We conclude that efficient severing utilizes two actin monomer-binding sites, and that the length of the WH2-containing segment is a critical functional determinant for severing.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Citoesqueleto de Actina / Gelsolina / Proteínas Mutantes Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: EMBO J Ano de publicação: 2006 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Citoesqueleto de Actina / Gelsolina / Proteínas Mutantes Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: EMBO J Ano de publicação: 2006 Tipo de documento: Article