Crosstalk between DnaA protein, the initiator of Escherichia coli chromosomal replication, and acidic phospholipids present in bacterial membranes

Int J Mol Sci. 2013 Apr 17;14(4):8517-37. doi: 10.3390/ijms14048517.


Anionic (i.e., acidic) phospholipids such as phosphotidylglycerol (PG) and cardiolipin (CL), participate in several cellular functions. Here we review intriguing in vitro and in vivo evidence that suggest emergent roles for acidic phospholipids in regulating DnaA protein-mediated initiation of Escherichia coli chromosomal replication. In vitro acidic phospholipids in a fluid bilayer promote the conversion of inactive ADP-DnaA to replicatively proficient ATP-DnaA, yet both PG and CL also can inhibit the DNA-binding activity of DnaA protein. We discuss how cellular acidic phospholipids may positively and negatively influence the initiation activity of DnaA protein to help assure chromosomal replication occurs once, but only once, per cell-cycle. Fluorescence microscopy has revealed that PG and CL exist in domains located at the cell poles and mid-cell, and several studies link membrane curvature with sub-cellular localization of various integral and peripheral membrane proteins. E. coli DnaA itself is found at the cell membrane and forms helical structures along the longitudinal axis of the cell. We propose that there is cross-talk between acidic phospholipids in the bacterial membrane and DnaA protein as a means to help control the spatial and temporal regulation of chromosomal replication in bacteria.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Bacterial Proteins / metabolism*
  • Cardiolipins / metabolism
  • Chromosomes, Bacterial / genetics
  • Chromosomes, Bacterial / metabolism
  • DNA Replication
  • DNA-Binding Proteins / metabolism*
  • Escherichia coli / genetics
  • Escherichia coli / growth & development
  • Escherichia coli / metabolism*
  • Escherichia coli Proteins / metabolism*
  • Genes, Bacterial
  • Membrane Fluidity
  • Membrane Lipids / metabolism
  • Mutation
  • Origin Recognition Complex
  • Phosphatidylglycerols / metabolism
  • Phospholipids / metabolism


  • Bacterial Proteins
  • Cardiolipins
  • DNA-Binding Proteins
  • DnaA protein, Bacteria
  • Escherichia coli Proteins
  • Membrane Lipids
  • OriC chromosomal replication origin
  • Origin Recognition Complex
  • Phosphatidylglycerols
  • Phospholipids