Tocilj, A., On, K. F., Yuan, Z., Sun, J., Elkayam, E., Li, H., Stillman, B., Joshua-Tor, L. (January 2017) Structure of the active form of human Origin Recognition Complex and its ATPase motor module. Elife, 6. ISSN 2050-084X (Electronic)2050-084X (Linking) (Public Dataset)
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Abstract
Binding of the Origin Recognition Complex (ORC) to origins of replication marks the first step in the initiation of replication of the genome in all eukaryotic cells. Here, we report the structure of the active form of human ORC determined by X-ray crystallography and cryo-electron microscopy. The complex is composed of an ORC1/4/5 motor module lobe in an organization reminiscent of the DNA polymerase clamp loader complexes. A second lobe contains the ORC2/3 subunits. The complex is organized as a double-layered shallow corkscrew, with the AAA+ and AAA+-like domains forming one layer, and the winged-helix domains (WHDs) forming a top layer. CDC6 fits easily between ORC1 and ORC2, completing the ring and the DNA-binding channel, forming an additional ATP hydrolysis site. Analysis of the ATPase activity of the complex provides a basis for understanding ORC activity as well as molecular defects observed in Meier-Gorlin Syndrome mutations.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | biophysics chromosomes genes human structural biology |
| Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > ATPase bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > origin recognition complex Investigative techniques and equipment > x ray crystallography |
| CSHL Authors: | |
| Communities: | CSHL Cancer Center Program > Gene Regulation and Cell Proliferation CSHL labs > Joshua-Tor lab CSHL labs > Stillman lab CSHL Cancer Center Program > Gene Regulation and Inheritance Program |
| Highlight: | Stillman, Bruce W. |
| Depositing User: | Matt Covey |
| Date: | 23 January 2017 |
| Date Deposited: | 26 Jan 2017 17:58 |
| Last Modified: | 26 Oct 2020 20:08 |
| PMCID: | PMC5291709 |
| Related URLs: | |
| Dataset ID: | |
| URI: | https://repository.cshl.edu/id/eprint/34048 |
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