Structure of the eukaryotic replicative CMG helicase suggests a pumpjack motion for translocation

Yuan, Zuanning; Bai, Lin; Sun, Jingchuan; Georgescu, Roxana; Liu, Jun; O'Donnell, Michael E.; Li, Huilin

doi:10.1038/nsmb.3170

Title: Structure of the eukaryotic replicative CMG helicase suggests a pumpjack motion for translocation

Journal Article · Mon Feb 08 00:00:00 EST 2016 · Nature Structural & Molecular Biology

DOI:https://doi.org/10.1038/nsmb.3170· OSTI ID:1335412

Yuan, Zuanning ^[1]; Bai, Lin ^[2]; Sun, Jingchuan ^[2]; Georgescu, Roxana ^[3]; Liu, Jun ^[4]; O'Donnell, Michael E. ^[3]; Li, Huilin ^[1]

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

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.

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Research Organization:: Brookhaven National Laboratory (BNL), Upton, NY (United States)

Sponsoring Organization:: USDOE; National Institute of Health

Grant/Contract Number:: SC0012704

OSTI ID:: 1335412

Report Number(s):: BNL-111966-2016-JA

Journal Information:: Nature Structural & Molecular Biology, Vol. 23, Issue 3; ISSN 1545-9993

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 103 works

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59 BASIC BIOLOGICAL SCIENCES
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Title: Structure of the eukaryotic replicative CMG helicase suggests a pumpjack motion for translocation

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