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

Autor: Maud Hertzog, Carine van Heijenoort, Louis Renault, Marcel Knossow, Dominique Didry, Eric Guittet, Marie-France Carlier, François-Xavier Cantrelle
Přispěvatelé: Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)
Jazyk: angličtina
Rok vydání: 2007
Předmět:
Models
Molecular
MESH: Thymosin
Protein Conformation
Molecular Sequence Data
Plasma protein binding
macromolecular substances
MESH: Amino Acid Sequence
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
MESH: Actins
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
Protein structure
MESH: Protein Conformation
History and Philosophy of Science
Animals
Humans
MESH: Protein Binding
MESH: Animals
Actin-binding protein
Amino Acid Sequence
Peptide sequence
Actin
030304 developmental biology
0303 health sciences
Binding Sites
MESH: Humans
MESH: Molecular Sequence Data
biology
General Neuroscience
030302 biochemistry & molecular biology
Actin remodeling
Actins
Cell biology
Thymosin
Profilin
MESH: Binding Sites
biology.protein
MDia1
Endothelium
Vascular
MESH: Endothelium
Vascular
Epidermis
MESH: Epidermis
MESH: Models
Molecular
Protein Binding
Zdroj: Annals of the New York Academy of Sciences
Annals of the New York Academy of Sciences, Wiley, 2007, 1112, pp.67-75. ⟨10.1196/annals.1415.037⟩
ISSN: 0077-8923
1749-6632
DOI: 10.1196/annals.1415.037⟩
Popis: International audience; 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.
Databáze: OpenAIRE
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