Structural highlights
3u9d is a 4 chain structure with sequence from Drome and Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , |
| Related: | 3sjh, 3u8x, 1sqk, 3u9z |
| Gene: | TMSB4, THYB4 (DROME) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[ACTS_RAT] Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. [TYB4_BOVIN] Plays an important role in the organization of the cytoskeleton. Binds to and sequesters actin monomers (G actin) and therefore inhibits actin polymerization (By similarity). Seraspenide inhibits the entry of hematopoietic pluripotent stem cells into the S-phase.
Publication Abstract from PubMed
beta-Thymosin (betaT) 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-beta4, or enhance motility by directing polarized filament assembly like Ciboulot betaT. We combined mutational, functional or structural analysis by X-ray crystallography, SAXS (small angle X-ray scattering) and NMR on Thymosin-beta4, Ciboulot, TetraThymosinbeta and the long WH2 domain of WASP-interacting protein. The latter sequesters G-actin with the same molecular mechanisms as Thymosin-beta4. Functionally different betaT/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 betaT and WH2 domains. The results open perspectives for elucidating the functions of betaT/WH2 domains in other modular proteins.
How a single residue in individual beta-thymosin/WH2 domains controls their functions in actin assembly.,Didry D, Cantrelle FX, Husson C, Roblin P, Moorthy AM, Perez J, Le Clainche C, Hertzog M, Guittet E, Carlier MF, van Heijenoort C, Renault L EMBO J. 2011 Dec 23. doi: 10.1038/emboj.2011.461. PMID:22193718[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Didry D, Cantrelle FX, Husson C, Roblin P, Moorthy AM, Perez J, Le Clainche C, Hertzog M, Guittet E, Carlier MF, van Heijenoort C, Renault L. How a single residue in individual beta-thymosin/WH2 domains controls their functions in actin assembly. EMBO J. 2011 Dec 23. doi: 10.1038/emboj.2011.461. PMID:22193718 doi:10.1038/emboj.2011.461
