5EBZ

Crystal structure of human IKK1

Summary for 5EBZ

• Entry DOI: 10.2210/pdb5ebz/pdb
• Descriptor: Inhibitor of nuclear factor kappa-B kinase subunit alpha, 2,3-di-O-sulfo-alpha-D-glucopyranose-(1-6)-alpha-D-glucopyranose-(1-6)-2,4-di-O-sulfo-alpha-D-glucopyranose, [(2S,3R,4S,5S,6R)-6-(hydroxymethyl)-2,4-bis(oxidanyl)-5-oxidanylsulfanyloxy-oxan-3-yl] hydrogen sulfate-(1-6)-(2S,3R,4R,5S,6R)-6-(hydroxymethyl)-5-oxidanylsulfanyloxy-oxane-2,3,4-triol-(1-6)-2-O-sulfo-alpha-D-glucopyranose-(1-6)-[(2R,3R,4R,5R,6S)-2-(hydroxymethyl)-5,6-bis(oxidanyl)-3-oxidanylsulfanyloxy-oxan-4-yl] hydrogen sulfate-(1-6)-[(2S,3R,4S,5R,6R)-6-(hydroxymethyl)-2,5-bis(oxidanyl)-4-oxidanylsulfanyloxy-oxan-3-yl] hydrogen sulfate-(1-6)-[(2R,3R,4R,5R,6S)-2-(hydroxymethyl)-5,6-bis(oxidanyl)-3-oxidanylsulfanyloxy-oxan-4-yl] hydrogen sulfate-(1-6)-2,4-di-O-sulfo-alpha-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: kinase, inhibitor, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 12
• Total formula weight: 933780.01

Authors

Polley, S.,Passos, D.,Huang, D.,Biswas, T.,Verma, I.,Lyumkis, D.,Ghosh, G. (deposition date: 2015-10-20, release date: 2016-11-02, Last modification date: 2024-03-06)

Primary citation

Polley, S.,Passos, D.O.,Huang, D.B.,Mulero, M.C.,Mazumder, A.,Biswas, T.,Verma, I.M.,Lyumkis, D.,Ghosh, G.
Structural Basis for the Activation of IKK1/ alpha.
Cell Rep, 17:1907-1914, 2016

PubMed Abstract: Distinct signaling pathways activate the NF-κB family of transcription factors. The canonical NF-κB-signaling pathway is mediated by IκB kinase 2/β (IKK2/β), while the non-canonical pathway depends on IKK1/α. The structural and biochemical bases for distinct signaling by these otherwise highly similar IKKs are unclear. We report single-particle cryoelectron microscopy (cryo-EM) and X-ray crystal structures of human IKK1 in dimeric (∼150 kDa) and hexameric (∼450 kDa) forms. The hexamer, which is the representative form in the crystal but comprises only ∼2% of the particles in solution by cryo-EM, is a trimer of IKK1 dimers. While IKK1 hexamers are not detectable in cells, the surface that supports hexamer formation is critical for IKK1-dependent cellular processing of p100 to p52, the hallmark of non-canonical NF-κB signaling. Comparison of this surface to that in IKK2 indicates significant divergence, and it suggests a fundamental role for this surface in signaling by these kinases through distinct pathways.

PubMed: 27851956
DOI: 10.1016/j.celrep.2016.10.067

Experimental method

X-RAY DIFFRACTION (4.5 Å)