How a single residue in individual β-thymosin/WH2 domains controls their functions in actin assembly. - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue EMBO Journal Année : 2012

How a single residue in individual β-thymosin/WH2 domains controls their functions in actin assembly.

Dominique Didry
  • Fonction : Auteur
Clotilde Husson
  • Fonction : Auteur
Pierre Roblin
  • Fonction : Auteur
Anna M Eswara Moorthy
  • Fonction : Auteur
Javier Perez
  • Fonction : Auteur
Christophe Le Clainche
Maud Hertzog
  • Fonction : Auteur
Marie-France Carlier
  • Fonction : Auteur
Louis Renault

Résumé

β-Thymosin (βT) and WH2 domains are widespread, intrinsically disordered actin-binding peptides that display significant sequence variability and different regulations of actin self-assembly in motile and morphogenetic processes. Here, we reveal the structural mechanisms by which, in their 1:1 stoichiometric complexes with actin, they either inhibit assembly by sequestering actin monomers like Thymosin-β4, or enhance motility by directing polarized filament assembly like Ciboulot βT. We combined mutational, functional or structural analysis by X-ray crystallography, SAXS (small angle X-ray scattering) and NMR on Thymosin-β4, Ciboulot, TetraThymosinβ and the long WH2 domain of WASP-interacting protein. The latter sequesters G-actin with the same molecular mechanisms as Thymosin-β4. Functionally different βT/WH2 domains differ by distinct dynamics of their C-terminal half interactions with G-actin pointed face. These C-terminal interaction dynamics are controlled by the strength of electrostatic interactions with G-actin. At physiological ionic strength, a single salt bridge with actin located next to their central LKKT/V motif induces G-actin sequestration in both isolated long βT and WH2 domains. The results open perspectives for elucidating the functions of βT/WH2 domains in other modular proteins.

Domaines

Chimie organique

Dates et versions

hal-00692490 , version 1 (30-04-2012)

Identifiants

Citer

Dominique Didry, Francois-Xavier Cantrelle, Clotilde Husson, Pierre Roblin, Anna M Eswara Moorthy, et al.. How a single residue in individual β-thymosin/WH2 domains controls their functions in actin assembly.. EMBO Journal, 2012, 31 (4), pp.1000-13. ⟨10.1038/emboj.2011.461⟩. ⟨hal-00692490⟩
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