6Z4X

Structure of the CAK complex form Chaetomium thermophilum bound to ATP-gamma-S

6Z4X の概要

• エントリーDOI: 10.2210/pdb6z4x/pdb
• 分子名称: CYCLIN domain-containing protein, Protein kinase domain-containing protein, RING-type domain-containing protein, ... (7 entities in total)
• 機能のキーワード: cak complex, kinase, tfiik, cell cycle, transcription, dna repair
• 由来する生物種: Chaetomium thermophilum; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 209148.62

構造登録者

Peissert, S.,Kuper, J.,Kisker, C. (登録日: 2020-05-26, 公開日: 2020-12-09, 最終更新日: 2024-01-24)

主引用文献

Peissert, S.,Schlosser, A.,Kendel, R.,Kuper, J.,Kisker, C.
Structural basis for CDK7 activation by MAT1 and Cyclin H.
Proc.Natl.Acad.Sci.USA, 117:26739-26748, 2020

PubMed Abstract: Cyclin-dependent kinase 7 (CDK7), Cyclin H, and the RING-finger protein MAT1 form the heterotrimeric CDK-activating kinase (CAK) complex which is vital for transcription and cell-cycle control. When associated with the general transcription factor II H (TFIIH) it activates RNA polymerase II by hyperphosphorylation of its C-terminal domain (CTD). In the absence of TFIIH the trimeric complex phosphorylates the T-loop of CDKs that control cell-cycle progression. CAK holds a special position among the CDK branch due to this dual activity and the dependence on two proteins for activation. We solved the structure of the CAK complex from the model organism at 2.6-Å resolution. Our structure reveals an intricate network of interactions between CDK7 and its two binding partners MAT1 and Cyclin H, providing a structural basis for the mechanism of CDK7 activation and CAK activity regulation. In vitro activity measurements and functional mutagenesis show that CDK7 activation can occur independent of T-loop phosphorylation and is thus exclusively MAT1-dependent by positioning the CDK7 T-loop in its active conformation.

PubMed: 33055219
DOI: 10.1073/pnas.2010885117

実験手法

X-RAY DIFFRACTION (2.98 Å)