The structure and function of MCM from archaeal M. Thermoautotrophicum

• Published in: Nature structural biology Vol. 10; no. 3; pp. 160 - 167
• Main Authors: Chen, Xiaojiang S, Fletcher, Ryan J, Bishop, Brooke E, Leon, Ronald P, Sclafani, Robert A, Ogata, Craig M
• Format: Journal Article
• Language: English
• Published: United States 01-03-2003
• Subjects: Amino Acid Sequence; Archaeal Proteins - chemistry; Archaeal Proteins - genetics; Archaeal Proteins - metabolism; Binding Sites; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Conserved Sequence; Crystallography, X-Ray; DNA - metabolism; DNA Helicases - chemistry; DNA Helicases - genetics; DNA Helicases - metabolism; DNA-Binding Proteins; Enzyme Stability; Imaging, Three-Dimensional; Methanobacterium - chemistry; Methanobacterium - metabolism; Models, Molecular; Molecular Sequence Data; Mutation; Peptide Fragments - chemistry; Peptide Fragments - genetics; Peptide Fragments - metabolism; Protein Conformation; Protein Folding; Protein Serine-Threonine Kinases - genetics; Protein Serine-Threonine Kinases - metabolism; Protein Structure, Tertiary; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins; Schizosaccharomyces pombe Proteins; Sequence Homology, Amino Acid; Structural Homology, Protein
• ISSN: 1072-8368; 2331-365X
• DOI: 10.1038/nsb893

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.