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PDBsum entry 2qby
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Replication/DNA
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PDB id
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2qby
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References listed in PDB file
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Key reference
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Title
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Replication origin recognition and deformation by a heterodimeric archaeal orc1 complex.
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Authors
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E.L.Dueber,
J.E.Corn,
S.D.Bell,
J.M.Berger.
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Ref.
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Science, 2007,
317,
1210-1213.
[DOI no: ]
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PubMed id
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Abstract
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The faithful duplication of genetic material depends on essential DNA
replication initiation factors. Cellular initiators form higher-order assemblies
on replication origins, using adenosine triphosphate (ATP) to locally remodel
duplex DNA and facilitate proper loading of synthetic replisomal components. To
better understand initiator function, we determined the 3.4 angstrom-resolution
structure of an archaeal Cdc6/Orc1 heterodimer bound to origin DNA. The
structure demonstrates that, in addition to conventional DNA binding elements,
initiators use their AAA+ ATPase domains to recognize origin DNA. Together these
interactions establish the polarity of initiator assembly on the origin and
induce substantial distortions into origin DNA strands. Biochemical and
comparative analyses indicate that AAA+/DNA contacts observed in the structure
are dynamic and evolutionarily conserved, suggesting that the complex forms a
core component of the basal initiation machinery.
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Figure 1.
Fig. 1. Initiator/origin complex. (A) Schematic of oriC2,
highlighting sequences recognized by Orc1-1, Orc1-2, and Orc1-3
paralogs (purple, gray, and teal arrows, respectively). The
direction of the purple arrows reflects the 5'-to-3' convention
of the mORB consensus sequence; the C2- and C3-site arrows
indicate the relative orientations of these repeats. The dashed
box denotes the C3/mORB dual site used in the cocrystal
structure. DUE, DNA unwinding element. (B) A cartoon of Orc1-1
illustrates the relative orientation of the initiator's
subdomains, with the ISM of the AAA+ domain in purple. ADP,
black sticks; magnesium ions, magenta sphere. (C) Global
architecture of the Orc1-1/Orc1-3  DNA complex.
Protein, purple and teal; DNA, orange; ADP, blacksticks;
magnesium ions, magenta spheres. (D) Electrostatic surface
representations of Orc1-1 and Orc1-3. The yellow line demarcates
the boundary between protomers.
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Figure 4.
Fig. 4. Initiator AAA+ interactions. (A) The AAA+ domains of
ATP-bound DnaA (Aquifex aeolicas, Protein Data Bank accession
number 2HCB) (24) assemble in a head-to-tail oligomer that
places the arginine finger of the box VII helix (gold) into the
ATPase active site of the adjacent protomer. (B) Stereo view of
the Orc1-1/Orc1-3 DNA complex
shows that contacts between adenosine diphosphate–bound
initiators and DNA orient successive AAA+ domains into a
similar, albeit more open, configuration to that of oligomerized
DnaA. For clarity, only initiator AAA+ domains are shown in (A)
and (B). Bound nucleotides (black) and magnesium ions (magenta)
are shown as spheres.
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The above figures are
reprinted
by permission from the AAAs:
Science
(2007,
317,
1210-1213)
copyright 2007.
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