Inhibitor B Kinase Binding by Inhibitor B Kinase

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• 作者：Devin Drew ; Eriko Shimada ; Kim Huynh ; Simon Bergqvist ; Rashmi Talwar ; Michael Karin ; Gourisankar Ghosh
• 刊名：Biochemistry
• 出版年：2007
• 出版时间：October 30, 2007
• 年：2007
• 卷：46
• 期：43
• 页码：12482 - 12490
• 全文大小：507K
• 年卷期：v.46,no.43(October 30, 2007)
• ISSN：1520-4995

文摘

Activation of a large multisubunit protein kinase, called the inhibitor B kinase (IKK) complex,is central to the induction of the family of transcription factors nuclear factor B. IKK is comprised oftwo catalytic subunits, IKK and IKK, and a regulatory IKK subunit. It is known that the catalyticIKK and regulatory IKK subunits associate through interactions mediated by the N-terminal region ofIKK and an 11-mer peptide located near the C-terminus of IKK. In this study, we have defined theminimal IKK segment that binds IKK and determined the binding affinity of the IKK/IKK complex.We identified that the N-terminal segment spanning residues 40-130 of IKK binds the IKK C-terminaldomain (residues 665-756) with K_d 25 nM. Several smaller N-terminal IKK deletion mutants withinthe N-terminal 130 residues, although in some cases retained IKK binding activity, showed a tendencyto aggregate and formed covalently linked complexes. However, expansion of the C-terminus of thesefragments to residue 210 completely changed the solution behavior of the IKK N-terminus withoutaffecting the IKK binding affinity. We also found that the IKK C-terminal domain formed a dimer insolution and the basic unit of the IKK/IKK complex was a dimer/dimer.