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Molecular basis for the dual function of Eps8 on actin dynamics: bundling and capping.
PLoS Biol ; 8(6): e1000387, 2010 Jun 01.
Article en En | MEDLINE | ID: mdl-20532239
ABSTRACT
Actin capping and cross-linking proteins regulate the dynamics and architectures of different cellular protrusions. Eps8 is the founding member of a unique family of capping proteins capable of side-binding and bundling actin filaments. However, the structural basis through which Eps8 exerts these functions remains elusive. Here, we combined biochemical, molecular, and genetic approaches with electron microscopy and image analysis to dissect the molecular mechanism responsible for the distinct activities of Eps8. We propose that bundling activity of Eps8 is mainly mediated by a compact four helix bundle, which is contacting three actin subunits along the filament. The capping activity is mainly mediated by a amphipathic helix that binds within the hydrophobic pocket at the barbed ends of actin blocking further addition of actin monomers. Single-point mutagenesis validated these modes of binding, permitting us to dissect Eps8 capping from bundling activity in vitro. We further showed that the capping and bundling activities of Eps8 can be fully dissected in vivo, demonstrating the physiological relevance of the identified Eps8 structural/functional modules. Eps8 controls actin-based motility through its capping activity, while, as a bundler, is essential for proper intestinal morphogenesis of developing Caenorhabditis elegans.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Actinas / Péptidos y Proteínas de Señalización Intracelular Límite: Humans Idioma: En Revista: PLoS Biol Asunto de la revista: BIOLOGIA Año: 2010 Tipo del documento: Article País de afiliación: Italia Pais de publicación: EEUU / ESTADOS UNIDOS / ESTADOS UNIDOS DA AMERICA / EUA / UNITED STATES / UNITED STATES OF AMERICA / US / USA

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Actinas / Péptidos y Proteínas de Señalización Intracelular Límite: Humans Idioma: En Revista: PLoS Biol Asunto de la revista: BIOLOGIA Año: 2010 Tipo del documento: Article País de afiliación: Italia Pais de publicación: EEUU / ESTADOS UNIDOS / ESTADOS UNIDOS DA AMERICA / EUA / UNITED STATES / UNITED STATES OF AMERICA / US / USA