1BU1

SRC FAMILY KINASE HCK SH3 DOMAIN


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.297 
  • R-Value Work: 0.233 
  • R-Value Observed: 0.233 

wwPDB Validation   3D Report Full Report


This is version 1.6 of the entry. See complete history


Literature

RT loop flexibility enhances the specificity of Src family SH3 domains for HIV-1 Nef.

Arold, S.O'Brien, R.Franken, P.Strub, M.P.Hoh, F.Dumas, C.Ladbury, J.E.

(1998) Biochemistry 37: 14683-14691

  • DOI: https://doi.org/10.1021/bi980989q
  • Primary Citation of Related Structures:  
    1BU1

  • PubMed Abstract: 

    Understanding the issue of specificity imposed in the interactions of SH3 domains has largely been addressed in studies investigating the interaction of proline-rich amino acid sequences derived from potential ligands for these domains. Although the interaction with this motif forms an essential platform in the binding of SH3 domains, in many cases little specificity is observed and the difference in affinity for so-called specific and nonspecific proline-rich sequences is not great. Furthermore, the binding interface between an SH3 domain and a protein ligand appears to encompass more interactions than are represented by that involving the proline-rich motif. Here we investigate the issue of specificity from the opposite point of view; namely, how does a ligand recognize different SH3 domains? We present the crystal structure of the unbound SH3 domain from hemopoietic cell kinase (Hck) which is a member of the Src family of tyrosine kinases. This structure reveals that, unlike the structures of other Src kinase SH3 domains, the RT loop region is highly mobile and lacks a network of hydrogen bonds that is elsewhere apparent. The RT loop has been shown to form a major part of the binding interface between SH3 domains and HIV-1 Nef. Thermodynamic data, derived from isothermal titration calorimetry, for the binding of Hck SH3 to HIV-1 Nef show that the binding of Hck (KD = 1.5 microM) is approximately an order of magnitude tighter than those of other Src family kinases that were investigated (Fyn, Lck, and Src). This increase in affinity is attributed to, among other effects, the inherent flexibility in the RT loop which does not require breaking the network of hydrogen bonds to adopt the conformation required for binding.


  • Organizational Affiliation

    Centre de Biochimie Structurale, UMR C9955 CNRS, U414 INSERM, Université Montpellier 1, France.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
PROTEIN (HEMOPOIETIC CELL KINASE)
A, B, C, D, E
A, B, C, D, E, F
57Homo sapiensMutation(s): 0 
Gene Names: HUMAN HCK
EC: 2.7.1.112
UniProt & NIH Common Fund Data Resources
Find proteins for P08631 (Homo sapiens)
Explore P08631 
Go to UniProtKB:  P08631
PHAROS:  P08631
GTEx:  ENSG00000101336 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP08631
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.297 
  • R-Value Work: 0.233 
  • R-Value Observed: 0.233 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 51.5α = 90
b = 106.15β = 90
c = 78.8γ = 90
Software Package:
Software NamePurpose
AMoREphasing
X-PLORrefinement
XDSdata reduction
XSCALEdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1998-11-11
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2018-04-04
    Changes: Data collection
  • Version 1.4: 2018-04-11
    Changes: Data collection
  • Version 1.5: 2021-06-30
    Changes: Data collection
  • Version 1.6: 2023-08-09
    Changes: Data collection, Database references, Refinement description