3SJH

Crystal Structure of a chimera containing the N-terminal domain (residues 8-29) of drosophila Ciboulot and the C-terminal domain (residues 18-44) of bovine Thymosin-beta4, bound to G-actin-ATP-Latrunculin A


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.75 Å
  • R-Value Free: 0.199 
  • R-Value Work: 0.169 
  • R-Value Observed: 0.171 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

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

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.

(2012) EMBO J 31: 1000-1013

  • DOI: https://doi.org/10.1038/emboj.2011.461
  • Primary Citation of Related Structures:  
    3SJH, 3U8X, 3U9D, 3U9Z

  • 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.


  • Organizational Affiliation

    Laboratoire d'Enzymologie et Biochimie Structurales, Centre de Recherche de Gif, CNRS, Gif-sur-Yvette, France.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Actin, alpha skeletal muscle375Oryctolagus cuniculusMutation(s): 0 
UniProt
Find proteins for P68135 (Oryctolagus cuniculus)
Explore P68135 
Go to UniProtKB:  P68135
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP68135
Sequence Annotations
Expand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Ciboulot/Thymosin beta-4 chimeric protein54Drosophila melanogasterBos taurus
This entity is chimeric
Mutation(s): 0 
Gene Names: cibEG:EG0007.11CG4944Dmel_CG4944
UniProt
Find proteins for O97428 (Drosophila melanogaster)
Explore O97428 
Go to UniProtKB:  O97428
Find proteins for P62326 (Bos taurus)
Explore P62326 
Go to UniProtKB:  P62326
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupsO97428P62326
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
LAR BindingDB:  3SJH IC50: min: 40, max: 110 (nM) from 3 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.75 Å
  • R-Value Free: 0.199 
  • R-Value Work: 0.169 
  • R-Value Observed: 0.171 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 67.644α = 90
b = 74.977β = 90
c = 86.393γ = 90
Software Package:
Software NamePurpose
XSCALEdata scaling
MOLREPphasing
REFMACrefinement
PDB_EXTRACTdata extraction

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-01-25
    Type: Initial release
  • Version 1.1: 2013-06-26
    Changes: Database references
  • Version 1.2: 2017-07-26
    Changes: Refinement description, Source and taxonomy
  • Version 1.3: 2023-09-13
    Changes: Data collection, Database references, Derived calculations, Refinement description