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Crystal structure of inhibitor of ?B kinase ?.

ABSTRACT: Inhibitor of ?B (I?B) kinase (IKK) phosphorylates I?B proteins, leading to their degradation and the liberation of nuclear factor ?B for gene transcription. Here we report the crystal structure of IKK? 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, ?-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 I?B? that restricts substrate specificity, and the ULD is also required for catalytic activity. The SDD mediates IKK? dimerization, but dimerization per se is not important for maintaining IKK? activity and instead is required for IKK? activation. Other IKK family members, IKK?, TBK1 and IKK-i, may have a similar trimodular architecture and function.

SUBMITTER: Xu G

PROVIDER: S-EPMC3081413 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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Crystal structure of inhibitor of κB kinase β.

Xu Guozhou G Lo Yu-Chih YC Li Qiubai Q Napolitano Gennaro G Wu Xuefeng X Jiang Xuliang X Dreano Michel M Karin Michael M Wu Hao H

Nature 20110320 7343

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 ...[more]

PMID: 21423167

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