title: 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. 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: Department of Biochemistry &Cell Biology, Stony Brook University, Stony Brook, New York, USA.|Biology Department, Brookhaven National Laboratory, Upton, New York, USA.
authors: Zuanning
authors: Z
authors: Yuan
authors: Biology Department, Brookhaven National Laboratory, Upton, New York, USA.
authors: Lin
authors: L
authors: Bai
authors: Biology Department, Brookhaven National Laboratory, Upton, New York, USA.
authors: Jingchuan
authors: J
authors: Sun
authors: DNA Replication Laboratory, Rockefeller University, New York, New York, USA.|Howard Hughes Medical Institute, Rockefeller University, New York, New York, USA.
authors: Roxana
authors: R
authors: Georgescu
authors: Department of Pathology and Laboratory Medicine, University of Texas Medical School at Houston, Houston, Texas, USA.
authors: Jun
authors: J
authors: Liu
authors: DNA Replication Laboratory, Rockefeller University, New York, New York, USA.|Howard Hughes Medical Institute, Rockefeller University, New York, New York, USA.
authors: Michael E
authors: ME
authors: O'Donnell
authors: Department of Biochemistry &Cell Biology, Stony Brook University, Stony Brook, New York, USA.|Biology Department, Brookhaven National Laboratory, Upton, New York, USA.
authors: Huilin
authors: H
authors: Li
mesh_terms: D020285:Cryoelectron Microscopy; D004265:DNA Helicases / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure*; D004261:DNA Replication; D008958:Models, Molecular; D011487:Protein Conformation; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000201:enzymology*
chemical_list: D004265:DNA Helicases