Structure and activation mechanism of the yeast RNA Pol II CTD kinase CTDK-1 complex

Proc Natl Acad Sci U S A. 2021 Jan 19;118(3):e2019163118. doi: 10.1073/pnas.2019163118.

Abstract

The C-terminal domain (CTD) kinase I (CTDK-1) complex is the primary RNA Polymerase II (Pol II) CTD Ser2 kinase in budding yeast. CTDK-1 consists of a cyclin-dependent kinase (CDK) Ctk1, a cyclin Ctk2, and a unique subunit Ctk3 required for CTDK-1 activity. Here, we present a crystal structure of CTDK-1 at 1.85-Å resolution. The structure reveals that, compared to the canonical two-component CDK-cyclin system, the third component Ctk3 of CTDK-1 plays a critical role in Ctk1 activation by stabilizing a key element of CDK regulation, the T-loop, in an active conformation. In addition, Ctk3 contributes to the assembly of CTDK-1 through extensive interactions with both Ctk1 and Ctk2. We also demonstrate that CTDK-1 physically and genetically interacts with the serine/arginine-like protein Gbp2. Together, the data in our work reveal a regulatory mechanism of CDK complexes.

Keywords: X-ray crystallography; cyclin-dependent kinase; mRNA processing; transcription.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence / genetics
  • Cell Nucleus / genetics
  • Cell Nucleus / ultrastructure
  • Crystallography, X-Ray
  • Cyclin-Dependent Kinases / genetics
  • Cyclin-Dependent Kinases / ultrastructure*
  • Cyclins / chemistry
  • Cyclins / ultrastructure
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / ultrastructure
  • Phosphorylation
  • Protein Conformation
  • Protein Kinases / genetics
  • Protein Kinases / ultrastructure*
  • RNA Polymerase II / genetics
  • RNA Polymerase II / ultrastructure*
  • RNA-Binding Proteins / genetics
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / ultrastructure
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / ultrastructure*
  • Transcription, Genetic*

Substances

  • CTDK-I protein complex, S cerevisiae
  • Cyclins
  • Gbp2 protein, S cerevisiae
  • Multiprotein Complexes
  • RNA-Binding Proteins
  • Saccharomyces cerevisiae Proteins
  • Protein Kinases
  • Cyclin-Dependent Kinases
  • RNA Polymerase II