How a single residue in individual β-thymosin/WH2 domains controls their functions in actin assembly.

摘要: β-Thymosin (βT) and WH2 domains are widespread, intrinsically disordered actin-binding peptides that display significant sequence variability different regulations of actin self-assembly in motile morphogenetic processes. Here, we reveal the structural mechanisms by which, their 1:1 stoichiometric complexes with actin, they either inhibit assembly sequestering monomers like Thymosin-β4, or enhance motility directing polarized filament Ciboulot βT. We combined mutational, functional analysis X-ray crystallography, SAXS (small angle scattering) NMR on Ciboulot, TetraThymosinβ long domain WASP-interacting protein. The latter sequesters G-actin same molecular as Thymosin-β4. Functionally βT/WH2 differ distinct dynamics C-terminal half interactions pointed face. These interaction controlled strength electrostatic G-actin. At physiological ionic strength, a single salt bridge located next to central LKKT/V motif induces sequestration both isolated βT domains. results open perspectives for elucidating functions other modular proteins.