An ABC transporter mediating the detechment of lipid-modified proteins from membranes

　　Lipoproteins in E. coli are synthesized with a signal peptide and then translocated across the inner (cytoplasmic) membrane by a Sec-mediated mechanism. When the precursor protein is translocated to the periplasmic side of the inner membrane, the N-terminal cysteine residue in the mature-protein region forms a thioether bond with diacylglyceride. This is followed by cleavage of the signal peptide by lipoprotein-specific signal-peptidase II, and, finally, aminoacylation of the cysteine residue. The result is a mature lipoprotein with a lipid-modified cysteine at its N terminus. This protein is then localized to either the inner or the inner or outer membrane, depending on the nature of the amino-acid residue next to the lipid-modified cysteine. Aspartate at this position makes lipoproteins specific to the inner membrane, whereas other amino acids direct lipoproteins to the outer membrane.
　　We have shown that the membrane localization of E.coli lipoproteins requires five Lol factors. A LolCDE complex belonging to the ATP-binding cassette (ABC) transporter superfamily catalyses the release of lipoproteins in a sorting-signal-dependent manner (1). LolA is a periplasmic chaperone and forms a water-soluble complex with outer-membrane-specific lipoproteins (2). As lipoproteins are water-insoluble because of their N-terminal lipid moiety, the formation of this complex is critical for crossing of the periplasm. Lipoprotein derivatives possessing an aspartate residue at position 2 remain in the inner membrane and do not form a complex with LolA. LolB, an outer-membrane lipoprotein, is a receptor for the LolA-lipoprotein complex and mediates the incorporation of lipoproteins into the outer membrane through the transient formation of a LolB-lipoprotein complex (3).
　　The Lol system is a general mechanism for lipoprotein localization in E.coli and evolutionarily conserved in other Gram-negative bacteria. The LolCDE complex differs mechanistically from all other ABC transportes as it is not involved in the transmembrane transport of substrates.

　　1.Yakushi, T., et al., (2000) Nature Cell Biol., 2, 212
　　2.Matsuyama, S., et al., (1995) EMBO J., 14, 3365
　　3.Matsuyama, S., et al., (1997) EMBO J., 16, 6947