5N4W

Crystal structure of the Cul2-Rbx1-EloBC-VHL ubiquitin ligase complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.90 Å
  • R-Value Free: 0.346 
  • R-Value Work: 0.302 
  • R-Value Observed: 0.304 

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This is version 1.3 of the entry. See complete history


Literature

Crystal Structure of the Cul2-Rbx1-EloBC-VHL Ubiquitin Ligase Complex.

Cardote, T.A.F.Gadd, M.S.Ciulli, A.

(2017) Structure 25: 901-911.e3

  • DOI: https://doi.org/10.1016/j.str.2017.04.009
  • Primary Citation of Related Structures:  
    5N4W

  • PubMed Abstract: 

    Cullin RING E3 ubiquitin ligases (CRLs) function in the ubiquitin proteasome system to catalyze the transfer of ubiquitin from E2 conjugating enzymes to specific substrate proteins. CRLs are large dynamic complexes and attractive drug targets for the development of small-molecule inhibitors and chemical inducers of protein degradation. The atomic details of whole CRL assembly and interactions that dictate subunit specificity remain elusive. Here we present the crystal structure of a pentameric CRL2 VHL complex, composed of Cul2, Rbx1, Elongin B, Elongin C, and pVHL. The structure traps a closed state of full-length Cul2 and a new pose of Rbx1 in a trajectory from closed to open conformation. We characterize hotspots and binding thermodynamics at the interface between Cul2 and pVHL-EloBC and identify mutations that contribute toward a selectivity switch for Cul2 versus Cul5 recognition. Our findings provide structural and biophysical insights into the whole Cul2 complex that could aid future drug targeting.


  • Organizational Affiliation

    Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cullin-2748Homo sapiensMutation(s): 0 
Gene Names: CUL2
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PHAROS:  Q13617
GTEx:  ENSG00000108094 
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UniProt GroupQ13617
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Von Hippel-Lindau disease tumor suppressorB [auth V]160Homo sapiensMutation(s): 0 
Gene Names: VHL
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PHAROS:  P40337
GTEx:  ENSG00000134086 
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UniProt GroupP40337
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
E3 ubiquitin-protein ligase RBX1C [auth R]102Homo sapiensMutation(s): 0 
Gene Names: RBX1RNF75ROC1
EC: 6.3.2
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GTEx:  ENSG00000100387 
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
Elongin-BD [auth B]104Homo sapiensMutation(s): 0 
Gene Names: ELOBTCEB2
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GTEx:  ENSG00000103363 
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Entity ID: 5
MoleculeChains Sequence LengthOrganismDetailsImage
Elongin-CE [auth C]97Homo sapiensMutation(s): 0 
Gene Names: ELOCTCEB1
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GTEx:  ENSG00000154582 
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Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.90 Å
  • R-Value Free: 0.346 
  • R-Value Work: 0.302 
  • R-Value Observed: 0.304 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 86.038α = 90
b = 190.962β = 90
c = 238.885γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
DIALSdata reduction
Aimlessdata scaling
PHASERphasing

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
European Research CouncilUnited KingdomERC-2012-StG-311460
Fundacao para a Ciencia e TecnologiaPortugalSFRH/BD/92417/2013

Revision History  (Full details and data files)

  • Version 1.0: 2017-06-07
    Type: Initial release
  • Version 1.1: 2017-06-21
    Changes: Database references
  • Version 1.2: 2018-10-24
    Changes: Advisory, Data collection, Derived calculations
  • Version 1.3: 2019-04-24
    Changes: Data collection, Source and taxonomy