title: Nucleotide-dependent conformational changes in the DnaA-like core of the origin recognition complex.
abstract: Structural details of initiator proteins for DNA replication have provided clues to the molecular events in this process. EM reconstructions of the Drosophila melanogaster origin recognition complex (ORC) reveal nucleotide-dependent conformational changes in the core of the complex. All five AAA+ domains in ORC contain a conserved structural element that, in DnaA, promotes formation of a right-handed helix, indicating that helical AAA+ substructures may be a feature of all initiators. A DnaA helical pentamer can be docked into ORC, and the location of Orc5 uniquely positions this core. The results suggest that ATP-dependent conformational changes observed in ORC derive from reorientation of the AAA+ domains. By analogy to the DNA-wrapping activity of DnaA, we posit that ORC together with Cdc6 prepares origin DNA for helicase loading through mechanisms related to the established pathway of prokaryotes.
authors.affiliation: Division of Biochemistry & Molecular Biology, Molecular & Cell Biology Department, 1 Barker Hall, University of California, Berkeley, California 94720, USA.
authors.forename: Megan G
authors.initials: MG
authors.lastname: Clarey
authors.forename: Jan P
authors.initials: JP
authors.lastname: Erzberger
authors.forename: Patricia
authors.initials: P
authors.lastname: Grob
authors.forename: Andres E
authors.initials: AE
authors.lastname: Leschziner
authors.forename: James M
authors.initials: JM
authors.lastname: Berger
authors.forename: Eva
authors.initials: E
authors.lastname: Nogales
authors.forename: Michael
authors.initials: M
authors.lastname: Botchan
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry* / Q000378:metabolism; D008854:Microscopy, Electron; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009711:Nucleotides / Q000378:metabolism*; D051738:Origin Recognition Complex / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
chemical_list: D001426:Bacterial Proteins; C504976:Cdc6 protein, Drosophila; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C066312:DnaA protein, Bacteria; D029721:Drosophila Proteins; D009711:Nucleotides; D051738:Origin Recognition Complex; D000255:Adenosine Triphosphate