5xf8 | pdb_00005xf8
Cryo-EM structure of the Cdt1-MCM2-7 complex in AMPPNP state
Structural highlights
FunctionMCM6_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. Once loaded onto DNA, double hexamers can slide on dsDNA in the absence of ATPase activity. Required for the entry in S phase and for cell division.[1] [2] Publication Abstract from PubMedThe minichromosome maintenance complex (MCM) hexameric complex (Mcm2-7) forms the core of the eukaryotic replicative helicase. During G1 phase, two Cdt1-Mcm2-7 heptamers are loaded onto each replication origin by the origin-recognition complex (ORC) and Cdc6 to form an inactive MCM double hexamer (DH), but the detailed loading mechanism remains unclear. Here we examine the structures of the yeast MCM hexamer and Cdt1-MCM heptamer from Saccharomyces cerevisiae. Both complexes form left-handed coil structures with a 10-15-A gap between Mcm5 and Mcm2, and a central channel that is occluded by the C-terminal domain winged-helix motif of Mcm5. Cdt1 wraps around the N-terminal regions of Mcm2, Mcm6 and Mcm4 to stabilize the whole complex. The intrinsic coiled structures of the precursors provide insights into the DH formation, and suggest a spring-action model for the MCM during the initial origin melting and the subsequent DNA unwinding. Open-ringed structure of the Cdt1-Mcm2-7 complex as a precursor of the MCM double hexamer.,Zhai Y, Cheng E, Wu H, Li N, Yung PY, Gao N, Tye BK Nat Struct Mol Biol. 2017 Mar;24(3):300-308. doi: 10.1038/nsmb.3374. Epub 2017, Feb 13. PMID:28191894[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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