Structural basis for ATP-dependent DnaA assembly and replication-origin remodeling.
In bacteria, the initiation of replication is controlled by DnaA, a member of the ATPases associated with various cellular activities (AAA+) protein superfamily. ATP binding allows DnaA to transition from a monomeric state into a large oligomeric complex that remodels replication origins, triggers duplex melting and facilitates replisome assembly. The crystal structure of AMP-PCP-bound DnaA reveals a right-handed superhelix defined by specific protein-ATP interactions. The observed quaternary structure of DnaA, along with topology footprint assays, indicates that a right-handed DNA wrap is formed around the initiation nucleoprotein complex. This model clarifies how DnaA engages and unwinds bacterial origins and suggests that additional, regulatory AAA+ proteins engage DnaA at filament ends. Eukaryotic and archaeal initiators also have the structural elements that promote open-helix formation, indicating that a spiral, open-ring AAA+ assembly forms the core element of initiators in all domains of life.
Erzberger
Jan P
JP
Division of Biochemistry and Molecular Biology, Molecular and Cell Biology Department, 327B Hildebrand Hall #3206, University of California, Berkeley, California 94720, USA.
Mott
Melissa L
ML
Berger
James M
JM
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D001419:Bacteria / Q000201:enzymology; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D011487:Protein Conformation; D018741:Replication Origin
D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C066312:DnaA protein, Bacteria; C005147:5'-adenylyl (beta,gamma-methylene)diphosphonate; D000255:Adenosine Triphosphate; D004247:DNA