The structure of bacterial DnaA: implications for general mechanisms underlying DNA replication initiation.
The initiation of DNA replication is a key event in the cell cycle of all organisms. In bacteria, replication initiation occurs at specific origin sequences that are recognized and processed by an oligomeric complex of the initiator protein DnaA. We have determined the structure of the conserved core of the Aquifex aeolicus DnaA protein to 2.7 A resolution. The protein comprises an AAA+ nucleotide-binding fold linked through a long, helical connector to an all-helical DNA-binding domain. The structure serves as a template for understanding the physical consequences of a variety of DnaA mutations, and conserved motifs in the protein suggest how two critical aspects of origin processing, DNA binding and homo-oligomerization, are mediated. The spatial arrangement of these motifs in DnaA is similar to that of the eukaryotic-like archaeal replication initiation factor Cdc6/Orc1, demonstrating that mechanistic elements of origin processing may be conserved across bacterial, archaeal and eukaryotic domains of life.
Erzberger
Jan P
JP
Biochemistry and Molecular Biology Division, Department of Molecular and Cell Biology, 229 Stanley Hall, University of California, Berkeley, CA 94720, USA.
Pirruccello
Michelle M
MM
Berger
James M
JM
D000595:Amino Acid Sequence; D019843:Archaeal Proteins / Q000737:chemistry / Q000235:genetics; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics; D018360:Crystallography, X-Ray; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment
D019843:Archaeal Proteins; D001426:Bacterial Proteins; C066503:CDC6 protein, S cerevisiae; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C066312:DnaA protein, Bacteria; D029701:Saccharomyces cerevisiae Proteins