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

doi:10.1038/nsmb1121

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 journal › Article › peer-review

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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 language	English (US)
Pages (from-to)	684-690
Number of pages	7
Journal	Nature Structural and Molecular Biology
Volume	13
Issue number	8
DOIs	https://doi.org/10.1038/nsmb1121
State	Published - Aug 2006

ASJC Scopus subject areas

Structural Biology
Molecular Biology

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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.",

author = "Clarey, {Megan G.} and Erzberger, {Jan P.} and Patricia Grob and Leschziner, {Andres E.} and Berger, {James M.} and Eva Nogales and Michael Botchan",

note = "Funding Information: where K is the total number of particles in each dataset and sµback2 is the average of the background noise variance. The resulting three-dimensional variance map was superposed to the corresponding three-dimensional reconstruction for both states of the ORC complex in Chimera47 (supported by US National Institutes of Health grant P41 RR-01081). Funding Information: We thank M. Gossen at the Max Delbruck Institute for numerous gifts of the Drosophila Orc5 monoclonal antibody, D. Remus for helpful discussions and the Office of Biological and Environmental Research of the US Department of Energy for support of E.N. E.N. is a Howard Hughes Medical Institute Investigator. This work was supported by US National Institutes of Health grant R39 CA 30490 to M.B.",

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doi = "10.1038/nsmb1121",

language = "English (US)",

volume = "13",

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AU - Clarey, Megan G.

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AU - Grob, Patricia

AU - Leschziner, Andres E.

AU - Berger, James M.

AU - Nogales, Eva

AU - Botchan, Michael

N1 - Funding Information: where K is the total number of particles in each dataset and sµback2 is the average of the background noise variance. The resulting three-dimensional variance map was superposed to the corresponding three-dimensional reconstruction for both states of the ORC complex in Chimera47 (supported by US National Institutes of Health grant P41 RR-01081). Funding Information: We thank M. Gossen at the Max Delbruck Institute for numerous gifts of the Drosophila Orc5 monoclonal antibody, D. Remus for helpful discussions and the Office of Biological and Environmental Research of the US Department of Energy for support of E.N. E.N. is a Howard Hughes Medical Institute Investigator. This work was supported by US National Institutes of Health grant R39 CA 30490 to M.B.

PY - 2006/8

Y1 - 2006/8

N2 - 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.

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

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