Lipoprotein-releasing ABC transporter LolCDE (LolCDE)

The Lipoprotein-releasing ABC transporter LolCDE is an essential protein complex located in the inner membrane of Gram-negative bacteria, serving as the initiator of the Lol (Localization of Lipoprotein) pathway (UniProt P0AE08, P0AE12, P0AE10). It is a member of the ATP-binding cassette (ABC) transporter family, composed of the membrane subunits LolC and LolE and the ATPase subunit LolD (PubMed: 30252931). The complex functions by utilizing the energy from ATP hydrolysis to extract lipoproteins from the inner membrane and transfer them to the periplasmic chaperone LolA for transport to the outer membrane (Nature, 2024, 630, 703–709). This process is fundamental for the biogenesis of the bacterial outer membrane and is critical for the viability of Gram-negative pathogens like Escherichia coli and Klebsiella pneumoniae. Because the Lol pathway is absent in Gram-positive bacteria and eukaryotic cells, LolCDE is a highly specific target for narrow-spectrum antibiotics. Recent breakthroughs have identified Lolamycin as a potent inhibitor of LolCDE, demonstrating the ability to selectively target pathogens while sparing the gut microbiome (Nature, 2024, 630, 703–709).

Other names

LolCDE complexLipoprotein localization machineryLolC-LolD-LolE complexLolCDE transporterLolCDE

Inhibition of the LolCDE complex prevents the ATP-dependent transfer of lipoproteins from the inner membrane to the periplasmic chaperone LolA, thereby disrupting the assembly of the bacterial outer membrane and leading to cell death (Nature, 2024, 630, 703–709).