Nature Structural & Molecular Biology
- 13, 684 - 690 (2006)
Published online: 9 July 2006; | doi:10.1038/nsmb1121
Nucleotide-dependent conformational changes in the DnaA-like core of the origin recognition complexMegan G Clarey1, Jan P Erzberger1, Patricia Grob1, Andres E Leschziner2, James M Berger1, Eva Nogales1, 2, 3 & Michael Botchan11
Division of Biochemistry & Molecular Biology, Molecular & Cell Biology Department, 1 Barker Hall, University of California, Berkeley, California 94720, USA. 2
Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, California 94720, USA. 3
Howard Hughes Medical Institute, Molecular and Cell Biology Department, LSA 355 #3200, University of California, Berkeley, California 94720-3200, USA.
Correspondence should be addressed to Michael Botchan mbotchan@berkeley.edu or Eva Nogales enogales@lbl.gov 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.
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