Details

Autor(en) / Beteiligte

• Rushe, Mia
• Silvian, Laura
• Bixler, Sarah
• Chen, Ling Ling
• Cheung, Anne
• Bowes, Scott
• Cuervo, Hernan
• Berkowitz, Steven
• Zheng, Timothy
• Guckian, Kevin
• Pellegrini, Maria
• Lugovskoy, Alexey

Titel

Structure of a NEMO/IKK-Associating Domain Reveals Architecture of the Interaction Site

Ist Teil von

• Structure (London), 2008-05, Vol.16 (5), p.798-808

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2008

Quelle

MEDLINE

Beschreibungen/Notizen

• The phosphorylation of IκB by the IKK complex targets it for degradation and releases NF-κB for translocation into the nucleus to initiate the inflammatory response, cell proliferation, or cell differentiation. The IKK complex is composed of the catalytic IKKα/β kinases and a regulatory protein, NF-κB essential modulator (NEMO; IKKγ). 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.