Structure, function, and evolution of the beta-thymosin/WH2 (WASP-Homology2) actin-binding module. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Annals of the New York Academy of Sciences Année : 2007

Structure, function, and evolution of the beta-thymosin/WH2 (WASP-Homology2) actin-binding module.

Marie-France Carlier
  • Fonction : Auteur
Maud Hertzog
  • Fonction : Auteur
Dominique Didry
  • Fonction : Auteur
Louis Renault
Marcel Knossow
  • Fonction : Auteur

Résumé

beta-thymosins are acknowledged G-actin sequesterers. However, in the recent years, the conserved beta-thymosins/WH2 actin-binding module, has been identified in a large number of proteins that all interact with actin and play diverse functions in cell motility. The functional evolution of the WH2 domain has been approached by a combination of structural and biochemical methods, using thymosin beta4 (Tbeta4) and Ciboulot, a 3 beta-thymosin repeat protein from Drosophila as models. Ciboulot binds actin like Tbeta4 but promotes actin assembly like profilin. The first repeat of Ciboulot (D1) has the profilin function of the whole protein. The crystal structure of Ciboulot-actin shows that the major interaction with G-actin lies in the N-terminal amphipathic helix of D1. By point mutagenesis the sequestering activity of Tbeta4 can be changed into a profilin activity. ((1)H, (15)N)-NMR studies show that the functional switch from inhibition to promotion of actin assembly is linked to a change in the dynamics of interaction of the central and C-terminal regions of the WH2 domain with subdomains 1 and 2 of G-actin. Further systematic mutagenesis studies have been performed by engineering a series of chimeras of Ciboulot and Tbeta4. Proteins displaying either profilin function or enhanced sequestering activity compared to Tbeta4 have been characterized. The results provide insight into the structural basis for the regulation of the multiple functions of the WH2 domain.

Dates et versions

hal-00260203 , version 1 (03-03-2008)

Identifiants

Citer

Marie-France Carlier, Maud Hertzog, Dominique Didry, Louis Renault, François-Xavier Cantrelle, et al.. Structure, function, and evolution of the beta-thymosin/WH2 (WASP-Homology2) actin-binding module.. Annals of the New York Academy of Sciences, 2007, 1112, pp.67-75. ⟨10.1196/annals.1415.037⟩. ⟨hal-00260203⟩
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