3BRT

NEMO/IKK association domain structure

Summary for 3BRT

• Entry DOI: 10.2210/pdb3brt/pdb
• Related: 3BRV
• Descriptor: Inhibitor of nuclear factor kappa-B kinase subunit beta,Inhibitor of nuclear factor kappa-B kinase subunit alpha, NF-kappa-B essential modulator (3 entities in total)
• Functional Keywords: nemo, ikk-gamma, fip3, ikkap1, nf-kb essential modulator, acetylation, atp-binding, cytoplasm, kinase, nucleotide-binding, phosphoprotein, polymorphism, serine/threonine-protein kinase, transferase, coiled coil, disease mutation, ectodermal dysplasia, host-virus interaction, nucleus, transcription, transcription regulation, transferase-transcription complex, transferase/transcription
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm : O15111 Q9Y6K9
• Total number of polymer chains: 4
• Total formula weight: 27136.65

Authors

Silvian, L.F. (deposition date: 2007-12-21, release date: 2008-04-22, Last modification date: 2024-02-21)

Primary citation

Rushe, M.,Silvian, L.,Bixler, S.,Chen, L.L.,Cheung, A.,Bowes, S.,Cuervo, H.,Berkowitz, S.,Zheng, T.,Guckian, K.,Pellegrini, M.,Lugovskoy, A.
Structure of a NEMO/IKK-Associating Domain Reveals Architecture of the Interaction Site.
Structure, 16:798-808, 2008

PubMed Abstract: 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.

PubMed: 18462684
DOI: 10.1016/j.str.2008.02.012

Experimental method

X-RAY DIFFRACTION (2.25 Å)