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PDBsum entry 7ctf
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Contents |
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102 a.a.
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302 a.a.
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592 a.a.
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406 a.a.
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373 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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Structural insight into the assembly and conformational activation of human origin recognition complex.
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Authors
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J.Cheng,
N.Li,
X.Wang,
J.Hu,
Y.Zhai,
N.Gao.
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Ref.
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Cell Discov, 2020,
6,
88.
[DOI no: ]
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PubMed id
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Abstract
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The function of the origin recognition complex (ORC) in DNA replication is
highly conserved in recognizing and marking the initiation sites. The detailed
molecular mechanisms by which human ORC is reconfigured into a state competent
for origin association remain largely unknown. Here, we present structural
characterizations of human ORC1-5 and ORC2-5 assemblies. ORC2-5 exhibits a
tightly autoinhibited conformation with the winged-helix domain of ORC2
completely blocking the central DNA-binding channel. The binding of ORC1
partially relieves the autoinhibitory effect of ORC2-5 through remodeling
ORC2-WHD, which makes ORC2-WHD away from the central channel creating a still
autoinhibited but more dynamic structure. In particular, the AAA+ domain of ORC1
is highly flexible to sample a variety of conformations from inactive to
potentially active states. These results provide insights into the detailed
mechanisms regulating the autoinhibition of human ORC and its subsequent
activation for DNA binding.
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