Nucleotide-dependent conformational changes in the DnaA-like core of the origin recognition complex

Megan G. Clarey, Jan P. Erzberger, Patricia Grob, Andres E. Leschziner, James M. Berger, Eva Nogales, Michael Botchan

Research output: Contribution to journalArticle

70 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)684-690
Number of pages7
JournalNature Structural and Molecular Biology
Volume13
Issue number8
DOIs
StatePublished - Aug 1 2006

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Origin Recognition Complex
Nucleotides
DNA Helicases
Drosophila melanogaster
DNA Replication
Adenosine Triphosphate
DNA
Proteins

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Nucleotide-dependent conformational changes in the DnaA-like core of the origin recognition complex. / Clarey, Megan G.; Erzberger, Jan P.; Grob, Patricia; Leschziner, Andres E.; Berger, James M.; Nogales, Eva; Botchan, Michael.

In: Nature Structural and Molecular Biology, Vol. 13, No. 8, 01.08.2006, p. 684-690.

Research output: Contribution to journalArticle

Clarey, Megan G. ; Erzberger, Jan P. ; Grob, Patricia ; Leschziner, Andres E. ; Berger, James M. ; Nogales, Eva ; Botchan, Michael. / Nucleotide-dependent conformational changes in the DnaA-like core of the origin recognition complex. In: Nature Structural and Molecular Biology. 2006 ; Vol. 13, No. 8. pp. 684-690.
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