title: Topology and structure of an engineered human cohesin complex bound to Pds5B.
abstract: The cohesin subunits Smc1, Smc3 and Scc1 form large tripartite rings which mediate sister chromatid cohesion and chromatin structure. These are thought to entrap DNA with the help of the associated proteins SA1/2 and Pds5A/B. Structural information is available for parts of cohesin, but analyses of entire cohesin complexes are limited by their flexibility. Here we generated a more rigid 'bonsai' cohesin by truncating the coiled coils of Smc1 and Smc3 and used single-particle electron microscopy, chemical crosslinking-mass spectrometry and in silico modelling to generate three-dimensional models of cohesin bound to Pds5B. The HEAT-repeat protein Pds5B forms a curved structure around the nucleotide-binding domains of Smc1 and Smc3 and bridges the Smc3-Scc1 and SA1-Scc1 interfaces. These results indicate that Pds5B forms an integral part of the cohesin ring by contacting all other cohesin subunits, a property that may reflect the complex role of Pds5 proteins in controlling cohesin-DNA interactions.
authors.affiliation: Department of Structural Dynamics, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, Göttingen 37077, Germany.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Hons
authors.affiliation: Research Institute of Molecular Pathology (IMP), Dr Bohr-Gasse 7, Vienna 1030, Austria.
authors.forename: Pim J
authors.initials: PJ
authors.lastname: Huis In 't Veld
authors.affiliation: Department of Structural Dynamics, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, Göttingen 37077, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Kaesler
authors.affiliation: Department of Biochemistry, Gene Center, Ludwig-Maximilian University, Feodor-Lynen-Strasse 25, Munich 81377, Germany.
authors.forename: Pascaline
authors.initials: P
authors.lastname: Rombaut
authors.affiliation: Research Institute of Molecular Pathology (IMP), Dr Bohr-Gasse 7, Vienna 1030, Austria.
authors.forename: Alexander
authors.initials: A
authors.lastname: Schleiffer
authors.affiliation: Department of Biochemistry, Gene Center, Ludwig-Maximilian University, Feodor-Lynen-Strasse 25, Munich 81377, Germany.
authors.forename: Franz
authors.initials: F
authors.lastname: Herzog
authors.affiliation: Department of Structural Dynamics, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, Göttingen 37077, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Stark
authors.affiliation: Research Institute of Molecular Pathology (IMP), Dr Bohr-Gasse 7, Vienna 1030, Austria.
authors.forename: Jan-Michael
authors.initials: JM
authors.lastname: Peters
mesh_terms: D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D003198:Computer Simulation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000378:metabolism*; D011485:Protein Binding; D000072417:Protein Domains; D015202:Protein Engineering; D014157:Transcription Factors / Q000378:metabolism*; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; D014157:Transcription Factors; D000097722:Cohesins; C118660:PDS5B protein, human