title: The structure and function of MCM from archaeal M. Thermoautotrophicum.
abstract: Eukaryotic chromosomal DNA is licensed for replication precisely once in each cell cycle. The mini-chromosome maintenance (MCM) complex plays a role in this replication licensing. We have determined the structure of a fragment of MCM from Methanobacterium thermoautotrophicum (mtMCM), a model system for eukaryotic MCM. The structure reveals a novel dodecameric architecture with a remarkably long central channel. The channel surface has an unusually high positive charge and binds DNA. We also show that the structure of the N-terminal fragment is conserved for all MCMs proteins despite highly divergent sequences, suggesting a common architecture for a similar task: gripping/remodeling DNA and regulating MCM activity. An mtMCM mutant protein equivalent to a yeast MCM5 (CDC46) protein with the bob1 mutation at its N terminus has only subtle structural changes, suggesting a Cdc7-bypass mechanism by Bob1 in yeast. Yeast bypass experiments using MCM5 mutant proteins support the hypothesis for the bypass mechanism.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado Health Science Center, School of Medicine, Denver, Colorado 80262, USA.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Fletcher
authors.forename: Brooke E
authors.initials: BE
authors.lastname: Bishop
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Leon
authors.forename: Robert A
authors.initials: RA
authors.lastname: Sclafani
authors.forename: Craig M
authors.initials: CM
authors.lastname: Ogata
authors.forename: Xiaojiang S
authors.initials: XS
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D019843:Archaeal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D004247:DNA / Q000378:metabolism; D004265:DNA Helicases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins; D004795:Enzyme Stability; D021621:Imaging, Three-Dimensional; D017014:Methanobacterium / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D017386:Sequence Homology, Amino Acid; D040681:Structural Homology, Protein
chemical_list: D019843:Archaeal Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D010446:Peptide Fragments; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C085711:mcm5 protein, S pombe; D004247:DNA; C489404:CDC7 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D004265:DNA Helicases; C403162:MCM protein, Methanobacterium thermoautotrophicum