3brt

From Proteopedia

proteopedia linkproteopedia link

Template:STRUCTURE 3brt

NEMO/IKK association domain structure

Overview

The phosphorylation of IkappaB by the IKK complex targets it for degradation and releases NF-kappaB for translocation into the nucleus to initiate the inflammatory response, cell proliferation, or cell differentiation. The IKK complex is composed of the catalytic IKKalpha/beta kinases and a regulatory protein, NF-kappaB essential modulator (NEMO; IKKgamma). 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.

About this Structure

3BRT is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structure of a NEMO/IKK-Associating Domain Reveals Architecture of the Interaction Site., Rushe M, Silvian L, Bixler S, Chen LL, Cheung A, Bowes S, Cuervo H, Berkowitz S, Zheng T, Guckian K, Pellegrini M, Lugovskoy A, Structure. 2008 May;16(5):798-808. PMID:18462684 Page seeded by OCA on Thu May 22 22:35:34 2008