PDBsum entry 6z4x

Transcription

PDB id: 6z4x

Contents

Protein chains

312 a.a.

322 a.a.

66 a.a.

Ligands

AGS ×2

Metals

_CL

_MG ×2

Waters ×1

PDB id:

6z4x

Name:

Transcription

Title:

Structure of the cak complex form chaetomium thermophilum bound to atp-gamma-s

Structure:

Cyclin domain-containing protein. Chain: a, d. Engineered: yes. Protein kinase domain-containing protein. Chain: b, e. Engineered: yes. Ring-type domain-containing protein. Chain: c, f. Engineered: yes

Source:

Chaetomium thermophilum. Organism_taxid: 209285. Expressed in: escherichia coli. Expression_system_taxid: 562. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_taxid: 562

Resolution:

2.98Å R-factor: 0.205 R-free: 0.246

Authors:

S.Peissert,J.Kuper,C.Kisker

Key ref:

S.Peissert et al. (2020). Structural basis for CDK7 activation by MAT1 and Cyclin H. Proc Natl Acad Sci U S A, 117, 26739-26748. PubMed id: 33055219 DOI: 10.1073/pnas.2010885117

Date:

26-May-20 Release date: 09-Dec-20

Protein chains

G0SH78  (G0SH78_CHATD) -  Cyclin-like domain-containing protein from Chaetomium thermophilum (strain DSM 1495 / CBS 144.50 / IMI 039719)

Seq: 425 a.a.

Struc: 312 a.a.

Protein chains

G0SFC6  (G0SFC6_CHATD) -  Protein kinase domain-containing protein from Chaetomium thermophilum (strain DSM 1495 / CBS 144.50 / IMI 039719)

Seq: 437 a.a.

Struc: 322 a.a.

Protein chains

G0SF48  (G0SF48_CHATD) -  RNA polymerase II transcription factor B subunit 3 from Chaetomium thermophilum (strain DSM 1495 / CBS 144.50 / IMI 039719)

Seq: 363 a.a.

Struc: 66 a.a.

Enzyme reactions

• Enzyme class: Chains B, E: E.C.2.7.11.22 - cyclin-dependent kinase.
• Reaction:
  1. L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H⁺
  2. L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1073/pnas.2010885117

Proc Natl Acad Sci U S A 117:26739-26748 (2020)

PubMed id: 33055219

Structural basis for CDK7 activation by MAT1 and Cyclin H.

S.Peissert, A.Schlosser, R.Kendel, J.Kuper, C.Kisker.

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 Chaetomium thermophilum 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.