2Y1M

Structure of native c-Cbl


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.67 Å
  • R-Value Free: 0.263 
  • R-Value Work: 0.218 
  • R-Value Observed: 0.221 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structural Basis for Autoinhibition and Phosphorylation-Dependent Activation of C-Cbl.

Dou, H.Buetow, L.Hock, A.Sibbet, G.J.Vousden, K.H.Huang, D.T.

(2012) Nat Struct Mol Biol 19: 184

  • DOI: https://doi.org/10.1038/nsmb.2231
  • Primary Citation of Related Structures:  
    2Y1M, 2Y1N, 4A49, 4A4B, 4A4C

  • PubMed Abstract: 

    Cbls are RING ubiquitin ligases that attenuate receptor tyrosine kinase (RTK) signal transduction. Cbl ubiquitination activity is stimulated by phosphorylation of a linker helix region (LHR) tyrosine residue. To elucidate the mechanism of activation, we determined the structures of human CBL, a CBL-substrate peptide complex and a phosphorylated-Tyr371-CBL-E2-substrate peptide complex, and we compared them with the known structure of a CBL-E2-substrate peptide complex. Structural and biochemical analyses show that CBL adopts an autoinhibited RING conformation, where the RING's E2-binding surface associates with CBL to reduce E2 affinity. Tyr371 phosphorylation activates CBL by inducing LHR conformational changes that eliminate autoinhibition, flip the RING domain and E2 into proximity of the substrate-binding site and transform the RING domain into an enhanced E2-binding module. This activation is required for RTK ubiquitination. Our results present a mechanism for regulation of c-Cbl's activity by autoinhibition and phosphorylation-induced activation.


  • Organizational Affiliation

    The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Glasgow, G61 1BD, United Kingdom.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
E3 UBIQUITIN-PROTEIN LIGASE
A, B, C, D, E
A, B, C, D, E, F
389Homo sapiensMutation(s): 0 
EC: 6.3.2
UniProt & NIH Common Fund Data Resources
Find proteins for P22681 (Homo sapiens)
Explore P22681 
Go to UniProtKB:  P22681
PHAROS:  P22681
GTEx:  ENSG00000110395 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP22681
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ZN
Query on ZN

Download Ideal Coordinates CCD File 
G [auth A]
H [auth A]
J [auth B]
K [auth B]
M [auth C]
G [auth A],
H [auth A],
J [auth B],
K [auth B],
M [auth C],
N [auth C],
P [auth D],
Q [auth D],
S [auth E],
T [auth E],
V [auth F],
W [auth F]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
CA
Query on CA

Download Ideal Coordinates CCD File 
I [auth A]
L [auth B]
O [auth C]
R [auth D]
U [auth E]
I [auth A],
L [auth B],
O [auth C],
R [auth D],
U [auth E],
X [auth F]
CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.67 Å
  • R-Value Free: 0.263 
  • R-Value Work: 0.218 
  • R-Value Observed: 0.221 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 146.8α = 90
b = 148.56β = 90
c = 348.21γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
MOSFLMdata reduction
SCALAdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-01-18
    Type: Initial release
  • Version 1.1: 2012-01-25
    Changes: Other
  • Version 1.2: 2012-02-15
    Changes: Other
  • Version 1.3: 2023-12-20
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description