+検索条件
-Structure paper
タイトル | Structural Basis for the Activation of IKK1/α. |
---|---|
ジャーナル・号・ページ | Cell Rep, Vol. 17, Issue 8, Page 1907-1914, Year 2016 |
掲載日 | 2016年11月15日 |
著者 | Smarajit Polley / Dario Oliveira Passos / De-Bin Huang / Maria Carmen Mulero / Anup Mazumder / Tapan Biswas / Inder M Verma / Dmitry Lyumkis / Gourisankar Ghosh / |
PubMed 要旨 | 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. |
リンク | Cell Rep / PubMed:27851956 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 4.5 - 5.9 Å |
構造データ | EMDB-8436, PDB-5tqw: EMDB-8437, PDB-5tqx: EMDB-8438, PDB-5tqy: EMDB-8439: PDB-5ebz: |
化合物 | ChemComp-5TL: |
由来 |
|
キーワード | Transferase/transferase inhibitor / kinase / inhibitor / Transferase-transferase inhibitor complex / TRANSFERASE / conserved helix-loop-helix / transcription / oncogene |