Structural Basis for ATP-dependent DnaA Assembly and Replication-Origin Remodeling

Nat Struct Mol Biol. 2006 Aug;13(8):676-83. doi: 10.1038/nsmb1115. Epub 2006 Jul 9.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / analogs & derivatives
  • Adenosine Triphosphate / chemistry
  • Adenosine Triphosphate / metabolism*
  • Amino Acid Sequence
  • Bacteria / enzymology
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Conserved Sequence
  • Crystallography, X-Ray
  • DNA / chemistry
  • DNA / metabolism
  • DNA Replication
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Models, Molecular
  • Protein Conformation
  • Replication Origin

Substances

  • Bacterial Proteins
  • DNA-Binding Proteins
  • DnaA protein, Bacteria
  • 5'-adenylyl (beta,gamma-methylene)diphosphonate
  • Adenosine Triphosphate
  • DNA

Associated data

  • PDB/2HCB