3qa8

Publication Abstract from PubMed

Inhibitor of kappaB (IkappaB) kinase (IKK) phosphorylates IkappaB proteins, leading to their degradation and the liberation of nuclear factor kappaB for gene transcription. Here we report the crystal structure of IKKbeta in complex with an inhibitor, at a resolution of 3.6 A. The structure reveals a trimodular architecture comprising the kinase domain, a ubiquitin-like domain (ULD) and an elongated, alpha-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 IkappaBalpha that restricts substrate specificity, and the ULD is also required for catalytic activity. The SDD mediates IKKbeta dimerization, but dimerization per se is not important for maintaining IKKbeta activity and instead is required for IKKbeta activation. Other IKK family members, IKKalpha, TBK1 and IKK-i, may have a similar trimodular architecture and function.

Crystal structure of inhibitor of kappaB kinase beta,Xu G, Lo YC, Li Q, Napolitano G, Wu X, Jiang X, Dreano M, Karin M, Wu H Nature. 2011 Mar 20. PMID:21423167^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.