3jc5

Structure of the eukaryotic replicative CMG helicase and pumpjack motionStructure of the eukaryotic replicative CMG helicase and pumpjack motion

3jc5, resolution 4.70Å Show:Asymmetric Unit Biological Assembly Structural highlights 3jc5 is a 10 chain structure with sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 4.7Å Experimental data: Check Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MCM5_YEAST Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity; specifically the MCM2-MCM5 association is proposed to be reversible and to mediate a open ring conformation which may facilitate DNA loading. Once loaded onto DNA, double hexamers can slide on dsDNA in the absence of ATPase activity. Publication Abstract from PubMed 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 A. 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. Structure of the eukaryotic replicative CMG helicase suggests a pumpjack motion for translocation.,Yuan Z, Bai L, Sun J, Georgescu R, Liu J, O'Donnell ME, Li H Nat Struct Mol Biol. 2016 Feb 8. doi: 10.1038/nsmb.3170. PMID:26854665 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.