3brt
From Proteopedia
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'''NEMO/IKK association domain structure''' | '''NEMO/IKK association domain structure''' | ||
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| + | ==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== | ==About this Structure== | ||
3BRT is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BRT OCA]. | 3BRT is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BRT OCA]. | ||
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| + | ==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:[http://www.ncbi.nlm.nih.gov/pubmed/18462684 18462684] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: I-kappa-B kinase]] | [[Category: I-kappa-B kinase]] | ||
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[[Category: Transferase]] | [[Category: Transferase]] | ||
[[Category: Transferase/transcription complex]] | [[Category: Transferase/transcription complex]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu May 22 22:35:34 2008'' |
Revision as of 19:35, 22 May 2008
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
Categories: Homo sapiens | I-kappa-B kinase | Protein complex | Silvian, L F. | Acetylation | Atp-binding | Coiled coil | Cytoplasm | Disease mutation | Ectodermal dysplasia | Fip3 | Host-virus interaction | Ikk-gamma | Ikkap1 | Kinase | Nemo | Nf-kb essential modulator | Nucleotide-binding | Nucleus | Phosphoprotein | Polymorphism | Serine/threonine-protein kinase | Transcription | Transcription regulation | Transferase | Transferase/transcription complex
