Structure of the active form of human Origin Recognition Complex and its ATPase motor module
- Cold Spring Harbor Laboratory, United States
- Cold Spring Harbor Laboratory/HHMI, United States
- Brookhaven National Laboratory/Stony Brook University, United States
- Brookhaven National Laboratory, United States
- Van Andel Research Institute, United States
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.
Article and author information
Author details
Funding
Howard Hughes Medical Institute
- Ante Tocilj
National Institute of General Medical Sciences (GM45436)
- Bruce Stillman
National Cancer Institute (PO1-CA13016)
- Ante Tocilj
National Institute of General Medical Sciences (GM111742)
- Huilin Li
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- John Kuriyan, Howard Hughes Medical Institute, University of California, Berkeley, United States
Version history
- Received: August 22, 2016
- Accepted: January 15, 2017
- Accepted Manuscript published: January 23, 2017 (version 1)
- Accepted Manuscript updated: January 24, 2017 (version 2)
- Version of Record published: February 3, 2017 (version 3)
Copyright
© 2017, Tocilj et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Structure of the active form of human Origin Recognition Complex and its ATPase motor module
eLife 6:e20818.
https://doi.org/10.7554/eLife.20818
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