Structure of a NEMO/IKK-Associating Domain Reveals Architecture of the Interaction Site
The phosphorylation of I{kappa}B by the IKK complex targets it for degradation and releases NF-{kappa}B for translocation into the nucleus to initiate the inflammatory response, cell proliferation, or cell differentiation. The IKK complex is composed of the catalytic IKK{alpha}/{beta} kinases and a regulatory protein, NF-{kappa}B essential modulator (NEMO; IKK{gamma}). NEMO associates with the unphosphorylated IKK kinase C termini and activates the IKK complex's catalytic activity. However, detailed structural information about the NEMO/IKK interaction is lacking. In this study, we have identified the minimal requirements for NEMO and IKK kinase association using a variety of biophysical techniques and have solved two crystal structures of the minimal NEMO/IKK kinase associating domains. We demonstrate that the NEMO core domain is a dimer that binds two IKK fragments and identify energetic hot spots that can be exploited to inhibit IKK complex formation with a therapeutic agent.
- Research Organization:
- Brookhaven National Laboratory (BNL) National Synchrotron Light Source
- Sponsoring Organization:
- Doe - Office Of Science
- DOE Contract Number:
- AC02-98CH10886
- OSTI ID:
- 959992
- Report Number(s):
- BNL--82978-2009-JA
- Journal Information:
- Structure, Journal Name: Structure Journal Issue: 5 Vol. 16
- Country of Publication:
- United States
- Language:
- English
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