6Z3U

Structure of the CAK complex form Chaetomium thermophilum

Summary for 6Z3U

• Entry DOI: 10.2210/pdb6z3u/pdb
• Descriptor: CYCLIN domain-containing protein, Protein kinase domain-containing protein, RING-type domain-containing protein, ... (5 entities in total)
• Functional Keywords: cak complex, kinase, tfiik, cell cycle, trnascription, dna repair, transcription
• Biological source: Chaetomium thermophilum (strain DSM 1495 / CBS 144.50 / IMI 039719); More
• Total number of polymer chains: 6
• Total formula weight: 208053.51

Authors

Peissert, S.,Kuper, J.,Kisker, C. (deposition date: 2020-05-22, release date: 2020-12-09, Last modification date: 2024-01-24)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.6 Å)