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

被引:72
作者
Clarey, Megan G.
Erzberger, Jan P.
Grob, Patricia
Leschziner, Andres E.
Berger, James M.
Nogales, Eva
Botchan, Michael
机构
[1] Univ Calif Berkeley, Div Biochem & Mol Biol, Dept Mol & Cellular Biochem, Berkeley, CA 94720 USA
[2] Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA
[3] Univ Calif Berkeley, Howard Hughes Med Inst, Dept Cell & Mol Biol, Berkeley, CA 94720 USA
关键词
D O I
10.1038/nsmb1121
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:684 / 690
页数:7
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