Multifunctionality of the beta-thymosin/WH2 module: G-actin sequestration, actin filament growth, nucleation, and severing.
The beta-thymosin/WH2 actin-binding module shows an amazing adaptation to multifunctionality. The beta-thymosins are genuine G-actin sequesterers of moderate affinity for G-actin, allowing an efficient regulation of the G-actin/F-actin ratio in cells by amplifying changes in the critical concentration for filament assembly. In contrast, the first beta-thymosin domain of the protein Ciboulot makes with G-actin a complex that supports filament growth, such as profilin-actin. We illustrate how the use of engineered chimeric proteins, actin-binding and polymerization assays, crystallographic, NMR, and SAXS structural approaches complement each other to decipher the molecular basis for the functional versatility of these intrinsically disordered domains when they form various 1:1 complexes with G-actin. Multifunctionality is expanded in tandem repeats of WH2 domains present in WASP family proteins and proteins involved in axis patterning like Cordon-Bleu and Spire. The tandem repeats generate new functions such as filament nucleation and severing, as well as barbed end binding, which add up to the G-actin sequestering activity. Novel regulation pathways in actin assembly emerge from these additional activities.
Centre de Recherche de Gif, Gif-sur-Yvette, France.
Clotilde
C
Husson
François-Xavier
FX
Cantrelle
Pierre
P
Roblin
Dominique
D
Didry
Kim Ho Diep
KH
Le
Javier
J
Perez
Eric
E
Guittet
Carine
C
Van Heijenoort
Louis
L
Renault
Marie-France
MF
Carlier
D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D003599:Cytoskeleton / Q000378:metabolism; D029721:Drosophila Proteins; D006801:Humans; D008840:Microfilament Proteins / Q000737:chemistry / Q000378:metabolism; D009419:Nerve Tissue Proteins; D051304:Profilins / Q000378:metabolism; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism; D053838:Scattering, Small Angle; D013947:Thymosin / Q000737:chemistry / Q000378:metabolism*; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000378:metabolism*; D000099201:Thymosin beta(4)
D000199:Actins; D029721:Drosophila Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D051304:Profilins; D011506:Proteins; D013947:Thymosin; D051300:Wiskott-Aldrich Syndrome Protein Family; D000099201:Thymosin beta(4); C414741:cib protein, Drosophila