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PDBsum entry 4xgc
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DNA binding protein
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PDB id
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4xgc
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Contents |
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281 a.a.
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567 a.a.
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402 a.a.
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310 a.a.
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37 a.a.
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19 a.a.
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440 a.a.
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References listed in PDB file
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Key reference
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Title
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Crystal structure of the eukaryotic origin recognition complex.
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Authors
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F.Bleichert,
M.R.Botchan,
J.M.Berger.
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Ref.
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Nature, 2015,
519,
321-326.
[DOI no: ]
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PubMed id
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Abstract
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Initiation of cellular DNA replication is tightly controlled to sustain genomic
integrity. In eukaryotes, the heterohexameric origin recognition complex (ORC)
is essential for coordinating replication onset. Here we describe the crystal
structure of Drosophila ORC at 3.5 Å resolution, showing that the 270
kilodalton initiator core complex comprises a two-layered notched ring in which
a collar of winged-helix domains from the Orc1-5 subunits sits atop a layer of
AAA+ (ATPases associated with a variety of cellular activities) folds. Although
canonical inter-AAA+ domain interactions exist between four of the six ORC
subunits, unanticipated features are also evident. These include highly
interdigitated domain-swapping interactions between the winged-helix folds and
AAA+ modules of neighbouring protomers, and a quasi-spiral arrangement of DNA
binding elements that circumnavigate an approximately 20 Å wide channel in the
centre of the complex. Comparative analyses indicate that ORC encircles DNA,
using its winged-helix domain face to engage the mini-chromosome maintenance 2-7
(MCM2-7) complex during replicative helicase loading; however, an observed
out-of-plane rotation of more than 90° for the Orc1 AAA+ domain disrupts
interactions with catalytic amino acids in Orc4, narrowing and sealing off entry
into the central channel. Prima facie, our data indicate that Drosophila ORC can
switch between active and autoinhibited conformations, suggesting a novel means
for cell cycle and/or developmental control of ORC functions.
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