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PDBsum entry 2hcb
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References listed in PDB file
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Key reference
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Title
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Structural basis for ATP-Dependent dnaa assembly and replication-Origin remodeling.
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Authors
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J.P.Erzberger,
M.L.Mott,
J.M.Berger.
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Ref.
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Nat Struct Biol, 2006,
13,
676-683.
[DOI no: ]
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PubMed id
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Abstract
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In bacteria, the initiation of replication is controlled by DnaA, a member of
the ATPases associated with various cellular activities (AAA+) protein
superfamily. ATP binding allows DnaA to transition from a monomeric state into a
large oligomeric complex that remodels replication origins, triggers duplex
melting and facilitates replisome assembly. The crystal structure of
AMP-PCP-bound DnaA reveals a right-handed superhelix defined by specific
protein-ATP interactions. The observed quaternary structure of DnaA, along with
topology footprint assays, indicates that a right-handed DNA wrap is formed
around the initiation nucleoprotein complex. This model clarifies how DnaA
engages and unwinds bacterial origins and suggests that additional, regulatory
AAA+ proteins engage DnaA at filament ends. Eukaryotic and archaeal initiators
also have the structural elements that promote open-helix formation, indicating
that a spiral, open-ring AAA+ assembly forms the core element of initiators in
all domains of life.
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Figure 1.
Figure 1. Structure of ATP-DnaA. (a) Overlay of the four DnaA
monomers in the asymmetric unit. The AAA+ module is colored
green and red (domains IIIA and IIIB, respectively); domain IV,
the DNA-binding element, is yellow. The ATP analog AMP-PCP is
shown as black sticks. The helix-turn-helix (HTH) motif in
domain IV and the N and C termini are labeled. (b) ATP-DnaA
forms a right-handed helical filament with 8[1] symmetry. Side
and axial views of four symmetry-related DnaA tetramers are
shown. Top, the four monomers in the asymmetric unit are colored
blue, green, orange and yellow. Bottom, identical view, but
protomers are colored by domain as in a.
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Figure 5.
Figure 5. Conformational changes induced by ATP binding. (a)
ATP-DnaA dimer (blue and gold) with ADP-DnaA (green; PDB entry
1L8Q) superposed on one subunit. (b) Detail, with arrows
indicating movement of the AAA+ lid (DnaA domain IIIB) required
to accommodate a steric clash that occurs in the ADP-DnaA AAA+
orientation (red circle). (c) Stereo view of the molecular
features of the ADP-to-ATP switch. The lid movement is
stabilized by interactions of the sensor II (SII) arginine with
the  -phosphate
and enables the box VII helix to engage the nucleotide through
the arginine finger (Arg230). Further stability is provided by
interactions of Glu280 with the ribose ring and of the box VII
residue Ser229 with Arg277.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(2006,
13,
676-683)
copyright 2006.
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