Crystal Structure of the Cohesin Gatekeeper Pds5 and in Complex with Kleisin Scc1

• Published in: Cell reports (Cambridge) 2016-03, Vol.14 (9), p.2108-2115
• Main Authors: Lee, Byung-Gil, Roig, Maurici B., Jansma, Marijke, Petela, Naomi, Metson, Jean, Nasmyth, Kim, Löwe, Jan
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Binding Sites; Cell Cycle Proteins - chemistry; Chromosomal Proteins, Non-Histone - chemistry; Crystallography, X-Ray; Fungal Proteins - chemistry; Models, Molecular; Protein Binding; Protein Conformation, alpha-Helical; Protein Interaction Domains and Motifs; Protein Structure, Quaternary; Saccharomycetales; Scc3; sister chromatid cohesion; Smc proteins; Structural Homology, Protein
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2016.02.020

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. [Display omitted] •The crystal structure of the cohesin subunit Pds5 was determined•The crystal structure of Pds5 in complex with Scc1 binding region was determined•Structure-based mutants in Pds5 and Scc1 were analyzed by coIP and ChIP-seq•Pds5 shows some similarity to Scc3, the other large HEAT repeat cohesin subunit Cohesin entraps DNA in a ring, facilitating sister chromatid cohesion during mitosis and meiosis. Lee et al. describe the structure of the cohesin subunit Pds5 in complex with Scc1, cohesin’s kleisin, mutants disrupting the Pds5:Scc1 interaction, and structural similarity to another cohesin subunit, Scc3.