3U9D

Crystal Structure of a chimera containing the N-terminal domain (residues 8-24) of drosophila Ciboulot and the C-terminal domain (residues 13-44) of bovine Thymosin-beta4, bound to G-actin-ATP

Summary for 3U9D

• Entry DOI: 10.2210/pdb3u9d/pdb
• Related: 1SQK 3SJH 3U8X 3U9Z
• Descriptor: Actin, alpha skeletal muscle, Thymosin beta-4, Chimeric protein, ADENOSINE-5'-TRIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: contractile protein, protein binding
• Biological source: Drosophila melanogaster (bovine,cow,domestic cattle,domestic cow); More
• Cellular location: Cytoplasm, cytoskeleton: P68136
• Total number of polymer chains: 4
• Total formula weight: 96713.61

Authors

Renault, L.,Husson, C.,Carlier, M.F.,Didry, D. (deposition date: 2011-10-18, release date: 2012-01-25, Last modification date: 2023-09-13)

Primary citation

Didry, D.,Cantrelle, F.X.,Husson, C.,Roblin, P.,Moorthy, A.M.,Perez, J.,Le Clainche, C.,Hertzog, M.,Guittet, E.,Carlier, M.F.,van Heijenoort, C.,Renault, L.
How a single residue in individual beta-thymosin/WH2 domains controls their functions in actin assembly.
Embo J., 31:1000-1013, 2012

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

PubMed: 22193718
DOI: 10.1038/emboj.2011.461

Experimental method

X-RAY DIFFRACTION (2.5 Å)