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-Structure paper
タイトル | The cryoelectron microscopy structure of the human CDK-activating kinase. |
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ジャーナル・号・ページ | Proc Natl Acad Sci U S A, Vol. 117, Issue 37, Page 22849-22857, Year 2020 |
掲載日 | 2020年9月15日 |
著者 | Basil J Greber / Juan M Perez-Bertoldi / Kif Lim / Anthony T Iavarone / Daniel B Toso / Eva Nogales / |
PubMed 要旨 | The human CDK-activating kinase (CAK), a complex composed of cyclin-dependent kinase (CDK) 7, cyclin H, and MAT1, is a critical regulator of transcription initiation and the cell cycle. It acts by ...The human CDK-activating kinase (CAK), a complex composed of cyclin-dependent kinase (CDK) 7, cyclin H, and MAT1, is a critical regulator of transcription initiation and the cell cycle. It acts by phosphorylating the C-terminal heptapeptide repeat domain of the RNA polymerase II (Pol II) subunit RPB1, which is an important regulatory event in transcription initiation by Pol II, and it phosphorylates the regulatory T-loop of CDKs that control cell cycle progression. Here, we have determined the three-dimensional (3D) structure of the catalytic module of human CAK, revealing the structural basis of its assembly and providing insight into CDK7 activation in this context. The unique third component of the complex, MAT1, substantially extends the interaction interface between CDK7 and cyclin H, explaining its role as a CAK assembly factor, and it forms interactions with the CDK7 T-loop, which may contribute to enhancing CAK activity. We have also determined the structure of the CAK in complex with the covalently bound inhibitor THZ1 in order to provide insight into the binding of inhibitors at the CDK7 active site and to aid in the rational design of therapeutic compounds. |
リンク | Proc Natl Acad Sci U S A / PubMed:32855301 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.8 - 3.3 Å |
構造データ | EMDB-22123, PDB-6xbz: EMDB-22131, PDB-6xd3: |
化合物 | ChemComp-MG: ChemComp-AGS: ChemComp-V0G: |
由来 |
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キーワード | TRANSFERASE / Kinase / transcription / cell cycle / complex |