The beta-thymosin/WH2 domain; structural basis for the switch from inhibition to promotion of actin assembly.
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.
Hertzog
Maud
M
Dynamique du Cytosquelette, Laboratoire d'Enzymologie et Biochimie Structurales, Institut Alfred Fessard, Centre National de la Recherche Scientifique, 91198 Gif-sur-Yvette, France.
van Heijenoort
Carine
C
Didry
Dominique
D
Gaudier
Martin
M
Coutant
Jérôme
J
Gigant
Benoît
B
Didelot
Gérard
G
Préat
Thomas
T
Knossow
Marcel
M
Guittet
Eric
E
Carlier
Marie-France
MF
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)
D000199:Actins; D029721:Drosophila Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D013947:Thymosin; D000099201:Thymosin beta(4); C414741:cib protein, Drosophila