title: Structure of Ctk3, a subunit of the RNA polymerase II CTD kinase complex, reveals a noncanonical CTD-interacting domain fold.
abstract: CTDK-I is a yeast kinase complex that phosphorylates the C-terminal repeat domain (CTD) of RNA polymerase II (Pol II) to promote transcription elongation. CTDK-I contains the cyclin-dependent kinase Ctk1 (homologous to human CDK9/CDK12), the cyclin Ctk2 (human cyclin K), and the yeast-specific subunit Ctk3, which is required for CTDK-I stability and activity. Here we predict that Ctk3 consists of a N-terminal CTD-interacting domain (CID) and a C-terminal three-helix bundle domain. We determine the X-ray crystal structure of the N-terminal domain of the Ctk3 homologue Lsg1 from the fission yeast Schizosaccharomyces pombe at 2.0 Å resolution. The structure reveals eight helices arranged into a right-handed superhelical fold that resembles the CID domain present in transcription termination factors Pcf11, Nrd1, and Rtt103. Ctk3 however shows different surface properties and no binding to CTD peptides. Together with the known structure of Ctk1 and Ctk2 homologues, our results lead to a molecular framework for analyzing the structure and function of the CTDK-I complex.
authors.affiliation: Max Planck Institute for Biophysical Chemistry, Department of Molecular Biology, Am Fassberg 11, Göttingen, 37077, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Mühlbacher
authors.affiliation: Gene Center Munich and Department of Biochemistry, Ludwig-Maximilians-Universität München, Feodor-Lynen-Str. 25, Munich, 81377, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Mayer
authors.affiliation: Gene Center Munich and Department of Biochemistry, Ludwig-Maximilians-Universität München, Feodor-Lynen-Str. 25, Munich, 81377, Germany.
authors.forename: Mai
authors.initials: M
authors.lastname: Sun
authors.affiliation: Gene Center Munich and Department of Biochemistry, Ludwig-Maximilians-Universität München, Feodor-Lynen-Str. 25, Munich, 81377, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Remmert
authors.affiliation: Gene Center Munich and Department of Biochemistry, Ludwig-Maximilians-Universität München, Feodor-Lynen-Str. 25, Munich, 81377, Germany.
authors.forename: Alan C M
authors.initials: AC
authors.lastname: Cheung
authors.affiliation: Max Planck Institute for Biophysical Chemistry, Department of Molecular Biology, Am Fassberg 11, Göttingen, 37077, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Niesser
authors.affiliation: Max Planck Institute for Biophysical Chemistry, Department of Molecular Biology, Am Fassberg 11, Göttingen, 37077, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Soeding
authors.affiliation: Max Planck Institute for Biophysical Chemistry, Department of Molecular Biology, Am Fassberg 11, Göttingen, 37077, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Cramer
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011494:Protein Kinases / Q000737:chemistry* / Q000648:ultrastructure*; D017434:Protein Structure, Tertiary; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D016415:Sequence Alignment
chemical_list: C118305:CTDK-I protein complex, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases
keywords: C-terminal repeat domain (CTD); RNA polymerase II; X-ray crystallography; cyclin-dependent kinase; gene transcription; structural biology