3QA8

Crystal Structure of inhibitor of kappa B kinase beta

Summary for 3QA8

• Entry DOI: 10.2210/pdb3qa8/pdb
• Related: 3QAD
• Descriptor: MGC80376 protein (1 entity in total)
• Functional Keywords: kinase ubiquitin-like domain, phosphorylation, kinase domain, ubiquitin-like domain, kinase, substrate binding, immune system, signaling protein
• Biological source: Xenopus laevis (clawed frog,common platanna,platanna)
• Total number of polymer chains: 8
• Total formula weight: 622987.06

Authors

Xu, G.,Lo, Y.C.,Li, Q.,Napolitano, G.,Wu, X.,Jiang, X.,Dreano, M.,Karin, M.,Wu, H. (deposition date: 2011-01-10, release date: 2011-04-06, Last modification date: 2024-05-22)

Primary citation

Xu, G.,Lo, Y.C.,Li, Q.,Napolitano, G.,Wu, X.,Jiang, X.,Dreano, M.,Karin, M.,Wu, H.
Crystal structure of inhibitor of kappa B kinase beta.
Nature, 472:325-330, 2011

PubMed Abstract: Inhibitor of κB (IκB) kinase (IKK) phosphorylates IκB proteins, leading to their degradation and the liberation of nuclear factor κB for gene transcription. Here we report the crystal structure of IKKβ in complex with an inhibitor, at a resolution of 3.6 Å. The structure reveals a trimodular architecture comprising the kinase domain, a ubiquitin-like domain (ULD) and an elongated, α-helical scaffold/dimerization domain (SDD). Unexpectedly, the predicted leucine zipper and helix-loop-helix motifs do not form these structures but are part of the SDD. The ULD and SDD mediate a critical interaction with IκBα that restricts substrate specificity, and the ULD is also required for catalytic activity. The SDD mediates IKKβ dimerization, but dimerization per se is not important for maintaining IKKβ activity and instead is required for IKKβ activation. Other IKK family members, IKKα, TBK1 and IKK-i, may have a similar trimodular architecture and function.

PubMed: 21423167
DOI: 10.1038/nature09853

Experimental method

X-RAY DIFFRACTION (3.6 Å)