Nucleotide-dependent conformational changes in the DnaA-like core of the origin recognition complex.
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.
Clarey
Megan G
MG
Division of Biochemistry & Molecular Biology, Molecular & Cell Biology Department, 1 Barker Hall, University of California, Berkeley, California 94720, USA.
Erzberger
Jan P
JP
Grob
Patricia
P
Leschziner
Andres E
AE
Berger
James M
JM
Nogales
Eva
E
Botchan
Michael
M
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
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