5TQY

CryoEM reconstruction of human IKK1, closed conformation 3

Summary for 5TQY

• Entry DOI: 10.2210/pdb5tqy/pdb
• Related: 5TQW 5TQX
• EMDB information: 8436 8437 8438 8439
• Descriptor: Inhibitor of nuclear factor kappa-B kinase subunit alpha (1 entity in total)
• Functional Keywords: kinase, conserved helix-loop-helix, transcription, oncogene, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 150293.89

Authors

Lyumkis, D.,Ghosh, G.,Polley, S.,Biswath, T.,Huang, D.,Passos, D.O. (deposition date: 2016-10-24, release date: 2016-11-09, Last modification date: 2024-03-13)

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

ELECTRON MICROSCOPY (5.2 Å)