title: Crystal Structure of the Cohesin Gatekeeper Pds5 and in Complex with Kleisin Scc1.
abstract: Sister chromatid cohesion is mediated by cohesin, whose Smc1, Smc3, and kleisin (Scc1) subunits form a ring structure that entraps sister DNAs. The ring is opened either by separase, which cleaves Scc1 during anaphase, or by a releasing activity involving Wapl, Scc3, and Pds5, which bind to Scc1 and open its interface with Smc3. We present crystal structures of Pds5 from the yeast L. thermotolerans in the presence and absence of the conserved Scc1 region that interacts with Pds5. Scc1 binds along the spine of the Pds5 HEAT repeat fold and is wedged between the spine and C-terminal hook of Pds5. We have isolated mutants that confirm the observed binding mode of Scc1 and verified their effect on cohesin by immunoprecipitation and calibrated ChIP-seq. The Pds5 structure also reveals architectural similarities to Scc3, the other large HEAT repeat protein of cohesin and, most likely, Scc2.
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
authors.forename: Byung-Gil
authors.initials: BG
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
authors.forename: Maurici B
authors.initials: MB
authors.lastname: Roig
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
authors.forename: Marijke
authors.initials: M
authors.lastname: Jansma
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
authors.forename: Naomi
authors.initials: N
authors.lastname: Petela
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
authors.forename: Jean
authors.initials: J
authors.lastname: Metson
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
authors.forename: Kim
authors.initials: K
authors.lastname: Nasmyth
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK. Electronic address: jyl@mrc-lmb.cam.ac.uk.
authors.forename: Jan
authors.initials: J
authors.lastname: Löwe
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000737:chemistry*; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry*; D018360:Crystallography, X-Ray; D005656:Fungal Proteins / Q000737:chemistry*; D008958:Models, Molecular; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D054730:Protein Interaction Domains and Motifs; D020836:Protein Structure, Quaternary; D004718:Saccharomycetales; D040681:Structural Homology, Protein
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D005656:Fungal Proteins
keywords: Scc3; Smc proteins; sister chromatid cohesion