Lipopolysaccharide transport protein B2FGC complex (LptB2FGC) (LptB2FGC)

The Lipopolysaccharide transport protein B2FGC complex (LptB2FGC) is an essential ATP-binding cassette (ABC) transporter located in the inner membrane of Gram-negative bacteria [1, 2]. It is responsible for the extraction of mature lipopolysaccharide (LPS) molecules from the inner membrane and their subsequent translocation across the periplasm to the outer membrane [2, 5]. The complex consists of two LptB ATPase subunits, the transmembrane proteins LptF and LptG, and the regulatory protein LptC [1, 4]. This machinery is critical for maintaining the integrity and impermeability of the bacterial outer membrane, which serves as a primary defense against environmental stressors and antibiotics [1, 6]. Because of its essential role in bacterial viability and its absence in eukaryotic cells, the LptB2FGC complex is a high-priority target for the development of novel antibiotics [5, 6]. Drugs like Zosurabalpin work by trapping LPS within the transporter's cavity, leading to toxic accumulation of LPS in the inner membrane and bacterial cell death [6]. Recent research has also identified that the complex possesses adenylate kinase activity, which may play a role in regulating its transport function [3, 7]. Inhibition of this complex not only kills the bacteria but also sensitizes them to other antibiotics by compromising the outer membrane barrier [12].

Other names

LptB2FG-C complexInner membrane lipopolysaccharide transporterLptB2FG complexLPS transport machinery

Inhibition of lipopolysaccharide extraction from the inner membrane by trapping the substrate within the transporter cavity and uncoupling ATP hydrolysis from transport [6].