title: The beta-thymosin/WH2 domain; structural basis for the switch from inhibition to promotion of actin assembly.
abstract: The widespread beta-thymosin/WH2 actin binding domain has versatile regulatory properties in actin dynamics and motility. beta-thymosins (isolated WH2 domain) maintain monomeric actin in a "sequestered" nonpolymerizable form. In contrast, when repeated in tandem or inserted in modular proteins, the beta-thymosin/WH2 domain promotes actin assembly at filament barbed ends, like profilin. The structural basis for these opposite functions is addressed using ciboulot, a three beta-thymosin repeat protein. Only the first repeat binds actin and possesses the function of ciboulot. The region that shows the strongest interaction with actin is an amphipathic N-terminal alpha helix, present in all beta-thymosin/WH2 domains, which recognizes the ATP bound actin structure and uses the shear motion of actin linked to ATP hydrolysis to control polymerization. Crystallographic ((1)H, (15)N), NMR, and mutagenetic data reveal that the weaker interaction of the C-terminal region of beta-thymosin/WH2 domain with actin accounts for the switch in function from inhibition to promotion of actin assembly.
authors.affiliation: Dynamique du Cytosquelette, Laboratoire d'Enzymologie et Biochimie Structurales, Institut Alfred Fessard, Centre National de la Recherche Scientifique, 91198 Gif-sur-Yvette, France.
authors.forename: Maud
authors.initials: M
authors.lastname: Hertzog
authors.forename: Carine
authors.initials: C
authors.lastname: van Heijenoort
authors.forename: Dominique
authors.initials: D
authors.lastname: Didry
authors.forename: Martin
authors.initials: M
authors.lastname: Gaudier
authors.forename: Jérôme
authors.initials: J
authors.lastname: Coutant
authors.forename: Benoît
authors.initials: B
authors.lastname: Gigant
authors.forename: Gérard
authors.initials: G
authors.lastname: Didelot
authors.forename: Thomas
authors.initials: T
authors.lastname: Préat
authors.forename: Marcel
authors.initials: M
authors.lastname: Knossow
authors.forename: Eric
authors.initials: E
authors.lastname: Guittet
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Carlier
mesh_terms: D000199:Actins / Q000096:biosynthesis* / Q000737:chemistry; D000818:Animals; D018360:Crystallography, X-Ray; D004330:Drosophila / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins; D009682:Magnetic Resonance Spectroscopy; D008840:Microfilament Proteins / Q000737:chemistry / Q000378:metabolism*; D009154:Mutation; D009419:Nerve Tissue Proteins; D017434:Protein Structure, Tertiary; D013947:Thymosin / Q000235:genetics / Q000378:metabolism*; D000099201:Thymosin beta(4)
chemical_list: D000199:Actins; D029721:Drosophila Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D013947:Thymosin; D000099201:Thymosin beta(4); C414741:cib protein, Drosophila