Structure of the eukaryotic replicative CMG helicase suggests a pumpjack motion for translocation
Abstract
The CMG helicase is composed of Cdc45, Mcm2–7 and GINS. Here we report the structure of the Saccharomyces cerevisiae CMG, determined by cryo-EM at a resolution of 3.7–4.8 Å. The structure reveals that GINS and Cdc45 scaffold the N tier of the helicase while enabling motion of the AAA+ C tier. CMG exists in two alternating conformations, compact and extended, thus suggesting that the helicase moves like an inchworm. The N-terminal regions of Mcm2–7, braced by Cdc45–GINS, form a rigid platform upon which the AAA+ C domains make longitudinal motions, nodding up and down like an oil-rig pumpjack attached to a stable platform. The Mcm ring is remodeled in CMG relative to the inactive Mcm2–7 double hexamer. In addition, the Mcm5 winged-helix domain is inserted into the central channel, thus blocking entry of double-stranded DNA and supporting a steric-exclusion DNA-unwinding model.
- Authors:
-
- Stony Brook Univ., NY (United States). Department of Biochemistry & Cell Biology; Brookhaven National Lab. (BNL), Upton, NY (United States). Biology Department
- Brookhaven National Lab. (BNL), Upton, NY (United States). Biology Department
- Rockefeller Univ., New York, NY (United States). DNA Replication Laboratory and Howard Hughes Medical Institute
- University of Texas Medical School at Houston, Houston, Texas (United States). Department of Pathology and Laboratory Medicine
- Publication Date:
- Research Org.:
- Brookhaven National Lab. (BNL), Upton, NY (United States)
- Sponsoring Org.:
- USDOE; National Institute of Health
- OSTI Identifier:
- 1335412
- Report Number(s):
- BNL-111966-2016-JA
Journal ID: ISSN 1545-9993
- Grant/Contract Number:
- SC0012704
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Nature Structural & Molecular Biology
- Additional Journal Information:
- Journal Volume: 23; Journal Issue: 3; Journal ID: ISSN 1545-9993
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; CMG; helicase; cryo-electron microscopy; replication; DNA translocation; strand exclusion
Citation Formats
Yuan, Zuanning, Bai, Lin, Sun, Jingchuan, Georgescu, Roxana, Liu, Jun, O'Donnell, Michael E., and Li, Huilin. Structure of the eukaryotic replicative CMG helicase suggests a pumpjack motion for translocation. United States: N. p., 2016.
Web. doi:10.1038/nsmb.3170.
Yuan, Zuanning, Bai, Lin, Sun, Jingchuan, Georgescu, Roxana, Liu, Jun, O'Donnell, Michael E., & Li, Huilin. Structure of the eukaryotic replicative CMG helicase suggests a pumpjack motion for translocation. United States. doi:10.1038/nsmb.3170.
Yuan, Zuanning, Bai, Lin, Sun, Jingchuan, Georgescu, Roxana, Liu, Jun, O'Donnell, Michael E., and Li, Huilin. Mon .
"Structure of the eukaryotic replicative CMG helicase suggests a pumpjack motion for translocation". United States. doi:10.1038/nsmb.3170. https://www.osti.gov/servlets/purl/1335412.
@article{osti_1335412,
title = {Structure of the eukaryotic replicative CMG helicase suggests a pumpjack motion for translocation},
author = {Yuan, Zuanning and Bai, Lin and Sun, Jingchuan and Georgescu, Roxana and Liu, Jun and O'Donnell, Michael E. and Li, Huilin},
abstractNote = {The CMG helicase is composed of Cdc45, Mcm2–7 and GINS. Here we report the structure of the Saccharomyces cerevisiae CMG, determined by cryo-EM at a resolution of 3.7–4.8 Å. The structure reveals that GINS and Cdc45 scaffold the N tier of the helicase while enabling motion of the AAA+ C tier. CMG exists in two alternating conformations, compact and extended, thus suggesting that the helicase moves like an inchworm. The N-terminal regions of Mcm2–7, braced by Cdc45–GINS, form a rigid platform upon which the AAA+ C domains make longitudinal motions, nodding up and down like an oil-rig pumpjack attached to a stable platform. The Mcm ring is remodeled in CMG relative to the inactive Mcm2–7 double hexamer. In addition, the Mcm5 winged-helix domain is inserted into the central channel, thus blocking entry of double-stranded DNA and supporting a steric-exclusion DNA-unwinding model.},
doi = {10.1038/nsmb.3170},
journal = {Nature Structural & Molecular Biology},
number = 3,
volume = 23,
place = {United States},
year = {2016},
month = {2}
}
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Works referencing / citing this record:
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