Structure of the active form of human Origin Recognition Complex and its ATPase motor module

Tocilj, A., On, K. F., Yuan, Z., Sun, J., Elkayam, E., Li, H., Stillman, B., Joshua-Tor, L. (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)

URL: https://www.ncbi.nlm.nih.gov/pubmed/28112645
DOI: 10.7554/eLife.20818

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 labs > Joshua-Tor lab
CSHL labs > Stillman lab
Highlight: Stillman, Bruce W.
Depositing User: Matt Covey
Date Deposited: 26 Jan 2017 17:58
Last Modified: 01 Sep 2017 15:32
PMCID: PMC5291709
Related URLs:
Dataset ID:
URI: http://repository.cshl.edu/id/eprint/34048

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving