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-Structure paper
Title | Structural Basis for the Activation of IKK1/α. |
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Journal, issue, pages | Cell Rep, Vol. 17, Issue 8, Page 1907-1914, Year 2016 |
Publish date | Nov 15, 2016 |
Authors | Smarajit Polley / Dario Oliveira Passos / De-Bin Huang / Maria Carmen Mulero / Anup Mazumder / Tapan Biswas / Inder M Verma / Dmitry Lyumkis / Gourisankar Ghosh / |
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 ...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. |
External links | Cell Rep / PubMed:27851956 / PubMed Central |
Methods | EM (single particle) / X-ray diffraction |
Resolution | 4.5 - 5.9 Å |
Structure data | EMDB-8436, PDB-5tqw: EMDB-8437, PDB-5tqx: EMDB-8438, PDB-5tqy: EMDB-8439: PDB-5ebz: |
Chemicals | ChemComp-5TL: |
Source |
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Keywords | Transferase/transferase inhibitor / kinase / inhibitor / Transferase-transferase inhibitor complex / TRANSFERASE / conserved helix-loop-helix / transcription / oncogene |