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-Structure paper
Title | Structural insight into the assembly and conformational activation of human origin recognition complex. |
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Journal, issue, pages | Cell Discov, Vol. 6, Issue 1, Page 88, Year 2020 |
Publish date | Nov 24, 2020 |
Authors | Jiaxuan Cheng / Ningning Li / Xiaohan Wang / Jiazhi Hu / Yuanliang Zhai / Ning Gao / |
PubMed Abstract | 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 ...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. |
External links | Cell Discov / PubMed:33298899 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.8 - 5.0 Å |
Structure data | EMDB-30462, PDB-7cte: EMDB-30463, PDB-7ctf: EMDB-30464, PDB-7ctg: EMDB-30467: |
Chemicals | ChemComp-ATP: |
Source |
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Keywords | REPLICATION / DNA replication initiation / Origin Recognition Complex (ORC) / cryo-EM / autoinhibition conformation / Origin Recognition Complex |