3FX0

Crystal structure of Human NEMO CC2_LZ domain


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.20 Å
  • R-Value Free: 0.306 
  • R-Value Work: 0.247 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structural basis for recognition of diubiquitins by NEMO.

Lo, Y.C.Lin, S.C.Rospigliosi, C.C.Conze, D.B.Wu, C.J.Ashwell, J.D.Eliezer, D.Wu, H.

(2009) Mol Cell 33: 602-615

  • DOI: https://doi.org/10.1016/j.molcel.2009.01.012
  • Primary Citation of Related Structures:  
    3FX0

  • PubMed Abstract: 

    NEMO is the regulatory subunit of the IkappaB kinase (IKK) in NF-kappaB activation, and its CC2-LZ region interacts with Lys63 (K63)-linked polyubiquitin to recruit IKK to receptor signaling complexes. In vitro, CC2-LZ also interacts with tandem diubiquitin. Here we report the crystal structure of CC2-LZ with two dimeric coiled coils representing CC2 and LZ, respectively. Surprisingly, mutagenesis and nuclear magnetic resonance experiments reveal that the binding sites for diubiquitins at LZ are composites of both chains and that each ubiquitin in diubiquitins interacts with symmetrical NEMO asymmetrically. For tandem diubiquitin, the first ubiquitin uses the conserved hydrophobic patch and the C-terminal tail, while the second ubiquitin uses an adjacent surface patch. For K63-linked diubiquitin, the proximal ubiquitin uses its conserved hydrophobic patch, while the distal ubiquitin mostly employs the C-terminal arm including the K63 linkage residue. These studies uncover the energetics and geometry for mutual recognition of NEMO and diubiquitins.


  • Organizational Affiliation

    Department of Biochemistry, Weill Cornell Medical College, New York, NY 10021, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
NF-kappa-B essential modulator
A, B
96Homo sapiensMutation(s): 0 
Gene Names: IKBKGFIP3NEMO
UniProt & NIH Common Fund Data Resources
Find proteins for Q9Y6K9 (Homo sapiens)
Explore Q9Y6K9 
Go to UniProtKB:  Q9Y6K9
PHAROS:  Q9Y6K9
GTEx:  ENSG00000269335 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9Y6K9
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.20 Å
  • R-Value Free: 0.306 
  • R-Value Work: 0.247 
  • Space Group: P 65
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 76.194α = 90
b = 76.194β = 90
c = 76.892γ = 120
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
SHELXphasing
CNSrefinement
PDB_EXTRACTdata extraction
ADSCdata collection
HKL-2000data reduction
SHELXDphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-04-07
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2017-11-01
    Changes: Refinement description
  • Version 1.3: 2024-02-21
    Changes: Data collection, Database references