title: Segrosome structure revealed by a complex of ParR with centromere DNA.
abstract: The stable inheritance of genetic material depends on accurate DNA partition. Plasmids serve as tractable model systems to study DNA segregation because they require only a DNA centromere, a centromere-binding protein and a force-generating ATPase. The centromeres of partition (par) systems typically consist of a tandem arrangement of direct repeats. The best-characterized par system contains a centromere-binding protein called ParR and an ATPase called ParM. In the first step of segregation, multiple ParR proteins interact with the centromere repeats to form a large nucleoprotein complex of unknown structure called the segrosome, which binds ParM filaments. pSK41 ParR binds a centromere consisting of multiple 20-base-pair (bp) tandem repeats to mediate both transcription autoregulation and segregation. Here we report the structure of the pSK41 segrosome revealed in the crystal structure of a ParR-DNA complex. In the crystals, the 20-mer tandem repeats stack pseudo-continuously to generate the full-length centromere with the ribbon-helix-helix (RHH) fold of ParR binding successive DNA repeats as dimer-of-dimers. Remarkably, the dimer-of-dimers assemble in a continuous protein super-helical array, wrapping the DNA about its positive convex surface to form a large segrosome with an open, solenoid-shaped structure, suggesting a mechanism for ParM capture and subsequent plasmid segregation.
authors: Department of Biochemistry and Molecular Biology, University of Texas, M.D. Anderson Cancer Center, Unit 1000, Houston, TX 77030, USA. maschuma@mdanderson.org
authors: Maria A
authors: MA
authors: Schumacher
authors: Tiffany C
authors: TC
authors: Glover
authors: Anthony J
authors: AJ
authors: Brzoska
authors: Slade O
authors: SO
authors: Jensen
authors: Thomas D
authors: TD
authors: Dunham
authors: Ronald A
authors: RA
authors: Skurray
authors: Neville
authors: N
authors: Firth
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002503:Centromere / Q000235:genetics* / Q000378:metabolism*; D020090:Chromosome Segregation; D018360:Crystallography, X-Ray; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008968:Molecular Conformation; D010957:Plasmids / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D013211:Staphylococcus aureus
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; C086169:ParR protein, bacteria; D012097:Repressor Proteins; D000251:Adenosine Triphosphatases