title: Structure of the eukaryotic MCM complex at 3.8 Å.
abstract: DNA replication in eukaryotes is strictly regulated by several mechanisms. A central step in this replication is the assembly of the heterohexameric minichromosome maintenance (MCM2-7) helicase complex at replication origins during G1 phase as an inactive double hexamer. Here, using cryo-electron microscopy, we report a near-atomic structure of the MCM2-7 double hexamer purified from yeast G1 chromatin. Our structure shows that two single hexamers, arranged in a tilted and twisted fashion through interdigitated amino-terminal domain interactions, form a kinked central channel. Four constricted rings consisting of conserved interior β-hairpins from the two single hexamers create a narrow passageway that tightly fits duplex DNA. This narrow passageway, reinforced by the offset of the two single hexamers at the double hexamer interface, is flanked by two pairs of gate-forming subunits, MCM2 and MCM5. These unusual features of the twisted and tilted single hexamers suggest a concerted mechanism for the melting of origin DNA that requires structural deformation of the intervening DNA.
authors.affiliation: Ministry of Education Key Laboratory of Protein Sciences, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Ningning
authors.initials: N
authors.lastname: Li
authors.affiliation: 1] Division of Life Science, Hong Kong Universityof Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China [2] Institute for Advanced Study, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Yuanliang
authors.initials: Y
authors.lastname: Zhai
authors.affiliation: Ministry of Education Key Laboratory of Protein Sciences, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yixiao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Ministry of Education Key Laboratory of Protein Sciences, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Wanqiu
authors.initials: W
authors.lastname: Li
authors.affiliation: Ministry of Education Key Laboratory of Protein Sciences, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Maojun
authors.initials: M
authors.lastname: Yang
authors.affiliation: Ministry of Education Key Laboratory of Protein Sciences, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Jianlin
authors.initials: J
authors.lastname: Lei
authors.affiliation: 1] Division of Life Science, Hong Kong Universityof Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China [2] Department of Molecular Biology and Genetics, College of Agriculture and Life Sciences, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Bik-Kwoon
authors.initials: BK
authors.lastname: Tye
authors.affiliation: Ministry of Education Key Laboratory of Protein Sciences, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Gao
mesh_terms: D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D002843:Chromatin / Q000737:chemistry; D017124:Conserved Sequence; D020285:Cryoelectron Microscopy; D004247:DNA / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry / Q000648:ultrastructure; D016193:G1 Phase; D064110:Minichromosome Maintenance Proteins / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure*; D008954:Models, Biological; D008958:Models, Molecular; D009097:Multienzyme Complexes / Q000737:chemistry / Q000648:ultrastructure; D009691:Nucleic Acid Denaturation; D011485:Protein Binding; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry* / Q000378:metabolism; D018741:Replication Origin; D012441:Saccharomyces cerevisiae / Q000737:chemistry* / Q000648:ultrastructure*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D000099272:Replisomes
chemical_list: D018797:Cell Cycle Proteins; D002843:Chromatin; D004247:DNA; D004259:DNA-Directed DNA Polymerase; D064110:Minichromosome Maintenance Proteins; D009097:Multienzyme Complexes; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D000099272:Replisomes; C069200:MCM5 protein, S cerevisiae; C069199:MCM2 protein, S cerevisiae