3BRT

NEMO/IKK association domain structure


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.25 Å
  • R-Value Free: 0.282 
  • R-Value Work: 0.238 
  • R-Value Observed: 0.240 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Structure of a NEMO/IKK-Associating Domain Reveals Architecture of the Interaction Site.

Rushe, M.Silvian, L.Bixler, S.Chen, L.L.Cheung, A.Bowes, S.Cuervo, H.Berkowitz, S.Zheng, T.Guckian, K.Pellegrini, M.Lugovskoy, A.

(2008) Structure 16: 798-808

  • DOI: https://doi.org/10.1016/j.str.2008.02.012
  • Primary Citation of Related Structures:  
    3BRT, 3BRV

  • PubMed Abstract: 

    The phosphorylation of IkappaB by the IKK complex targets it for degradation and releases NF-kappaB for translocation into the nucleus to initiate the inflammatory response, cell proliferation, or cell differentiation. The IKK complex is composed of the catalytic IKKalpha/beta kinases and a regulatory protein, NF-kappaB essential modulator (NEMO; IKKgamma). NEMO associates with the unphosphorylated IKK kinase C termini and activates the IKK complex's catalytic activity. However, detailed structural information about the NEMO/IKK interaction is lacking. In this study, we have identified the minimal requirements for NEMO and IKK kinase association using a variety of biophysical techniques and have solved two crystal structures of the minimal NEMO/IKK kinase associating domains. We demonstrate that the NEMO core domain is a dimer that binds two IKK fragments and identify energetic hot spots that can be exploited to inhibit IKK complex formation with a therapeutic agent.


  • Organizational Affiliation

    Biogen Idec Inc., Cambridge, MA 02142, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Inhibitor of nuclear factor kappa-B kinase subunit beta,Inhibitor of nuclear factor kappa-B kinase subunit alpha
A, C
47Homo sapiensMutation(s): 0 
Gene Names: IKBKBIKKB
EC: 2.7.11.10
UniProt & NIH Common Fund Data Resources
Find proteins for O15111 (Homo sapiens)
Explore O15111 
Go to UniProtKB:  O15111
PHAROS:  O15111
GTEx:  ENSG00000213341 
Find proteins for O14920 (Homo sapiens)
Explore O14920 
Go to UniProtKB:  O14920
PHAROS:  O14920
GTEx:  ENSG00000104365 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupsO15111O14920
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
NF-kappa-B essential modulator
B, D
68Homo sapiensMutation(s): 1 
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: 2.25 Å
  • R-Value Free: 0.282 
  • R-Value Work: 0.238 
  • R-Value Observed: 0.240 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 41.869α = 90
b = 105.556β = 90
c = 56.707γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
CBASSdata collection
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-04-22
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2017-08-02
    Changes: Advisory, Source and taxonomy
  • Version 1.3: 2021-10-20
    Changes: Advisory, Database references
  • Version 1.4: 2024-02-21
    Changes: Data collection