Segrosome structure revealed by a complex of ParR with centromere DNA

• Published in: Nature 2007-12, Vol.450 (7173), p.1268-1271
• Main Authors: Schumacher, Maria A, Glover, Tiffany C, Brzoska, Anthony J, Jensen, Slade O, Dunham, Thomas D, Skurray, Ronald A, Firth, Neville
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphatases - genetics; Adenosine Triphosphatases - metabolism; Bacterial Proteins - chemistry; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Binding sites; Biological and medical sciences; Cellular biology; Centromere - genetics; Centromere - metabolism; Chromosome Segregation; Crystal structure; Crystalline structure; Crystallography, X-Ray; Crystals; Deoxyribonucleic acid; DNA; DNA, Bacterial - chemistry; DNA, Bacterial - genetics; DNA, Bacterial - metabolism; Fundamental and applied biological sciences. Psychology; Humanities and Social Sciences; letter; Models, Molecular; Molecular biophysics; Molecular Conformation; multidisciplinary; Plasmids - chemistry; Plasmids - genetics; Plasmids - metabolism; Proteins; Repressor Proteins - chemistry; Repressor Proteins - genetics; Repressor Proteins - metabolism; Science; Science (multidisciplinary); Staphylococcus aureus; Structure in molecular biology
• ISSN: 0028-0836; 1476-4687; 1476-4679
• DOI: 10.1038/nature06392

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.