Structural insight into the assembly and conformational activation of human origin recognition complex
| Autor: | Xiaohan Wang, Yuanliang Zhai, Ning Gao, Jiazhi Hu, Ningning Li, Jiaxuan Cheng |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0303 health sciences
Chemistry DNA replication Cell Biology Biochemistry Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cryoelectron microscopy Genetics Biophysics Origin recognition complex ORC1 Molecular Biology ORC2 Origin selection 030217 neurology & neurosurgery Function (biology) DNA 030304 developmental biology |
| Zdroj: | Cell Discovery |
| ISSN: | 2056-5968 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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