2MS4

Cyclophilin a complexed with a fragment of crk-ii


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Cyclophilin A promotes cell migration via the Abl-Crk signaling pathway.

Saleh, T.Jankowski, W.Sriram, G.Rossi, P.Shah, S.Lee, K.B.Cruz, L.A.Rodriguez, A.J.Birge, R.B.Kalodimos, C.G.

(2016) Nat Chem Biol 12: 117-123

  • DOI: https://doi.org/10.1038/nchembio.1981
  • Primary Citation of Related Structures:  
    2MS4

  • PubMed Abstract: 

    Cyclophilin A (CypA) is overexpressed in a number of human cancer types, but the mechanisms by which the protein promotes oncogenic properties of cells are not understood. Here we demonstrate that CypA binds the CrkII adaptor protein and prevents it from switching to the inhibited state. CrkII influences cell motility and invasion by mediating signaling through its SH2 and SH3 domains. CrkII Tyr221 phosphorylation by the Abl or EGFR kinases induces an inhibited state of CrkII by means of an intramolecular SH2-pTyr221 interaction, causing signaling interruption. We show that the CrkII phosphorylation site constitutes a binding site for CypA. Recruitment of CypA sterically restricts the accessibility of Tyr221 to kinases, thereby suppressing CrkII phosphorylation and promoting the active state. Structural, biophysical and in vivo data show that CypA augments CrkII-mediated signaling. A strong stimulation of cell migration is observed in cancer cells wherein both CypA and CrkII are greatly upregulated.


  • Organizational Affiliation

    Department of Biochemistry, Molecular Biology &Biophysics, University of Minnesota, Minneapolis, Minnesota, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Peptidyl-prolyl cis-trans isomerase A165Homo sapiensMutation(s): 0 
Gene Names: PPIACYPA
EC: 5.2.1.8
UniProt & NIH Common Fund Data Resources
Find proteins for P62937 (Homo sapiens)
Explore P62937 
Go to UniProtKB:  P62937
PHAROS:  P62937
GTEx:  ENSG00000196262 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP62937
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Peptide9Homo sapiensMutation(s): 0 
Gene Names: CRK
UniProt & NIH Common Fund Data Resources
Find proteins for P46108 (Homo sapiens)
Explore P46108 
Go to UniProtKB:  P46108
PHAROS:  P46108
GTEx:  ENSG00000167193 
Entity Groups  
UniProt GroupP46108
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the lowest energy 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2015-09-09
    Type: Initial release
  • Version 1.1: 2015-12-16
    Changes: Database references
  • Version 1.2: 2015-12-30
    Changes: Database references
  • Version 1.3: 2016-02-03
    Changes: Database references