Crystal Structure of a Human IaB Kinase ß Asymmetric Dimer
News Jun 27, 2013
Phosphorylation of inhibitor of nuclear transcription factor B (IB) by IB kinase (IKK) triggers the degradation of IB and migration of cytoplasmic B to the nucleus where it promotes the transcription of its target genes. Activation of IKK is achieved by phosphorylation of its main subunit, IKK at the activation loop sites. Here we report the 2.8 Å resolution crystal structure of human IKKhIKK which is partially phosphorylated and bound to the staurosporine analog K252a. The hIKK protomer adopts a trimodular structure that closely resembles that from Xenopus laevis (xIKK: an N-terminal kinase domain (KD), a central ubiquitinlike domain (ULD), and a C-terminal dimerization domain (SDD). Although hIKK and xIKK utilize a similar dimerization mode, their overall geometries are distinct. In contrast to the structure resembling closed shears reported previously for xIKK hIKK exists as an open asymmetric dimer in which the two KDs are further apart, with one in an active and the other in an inactive conformation. Dimer interactions are limited to the C-terminal six-helix bundle that acts as a hinge between the two subunits. The observed domain movements in the structures of IKK may represent transphosphorylation steps that accompany IKK activation.
This article was published online in The Journal of Biological Chemistry and is free to access.
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