Sequestration of Origins of Chromosome Replication in Escherichia coli by Lipid Compartments: The Pocket Hypothesis

After initiation of chromosome replication in Escherichia coli, the newly replicated, hemi-methylated origins of replication are exempt from both re-initiation and methylation for up to a third of the generation time. In the model proposed here, the exemption from methylation is attributed to the phospholipid preferences of proteins binding hemi-methylated origins to membrane; these proteins associate with unsaturated phosphatidylethanolamine which forms structures with small radii of curvature; hence, a lipid compartment or "pocket" forms around the origin making it inaccessible to cytoplasmic enzymes such as Dam methyltransferase. Since autolysins and peptidoglycan-synthesizing enzymes are sensitive to lipid composition, peptidoglycan synthesis is stimulated around this compartment and creates structures obtained in membrane fractionation that specifically bind hemi-methylated origins.