Lipopolysaccharide transport protein B2FGC complex (LptB2FGC)

The Lipopolysaccharide transport protein B2FGC complex is an essential ATP-binding cassette (ABC) transporter located in the inner membrane of Gram-negative bacteria [1, 4]. It consists of two LptB ATPase subunits, the transmembrane proteins LptF and LptG, and the bitopic protein LptC [4, 13]. This complex is responsible for the first step of the lipopolysaccharide (LPS) transport pathway: extracting mature LPS from the outer leaflet of the inner membrane and transferring it to a periplasmic protein bridge for delivery to the outer membrane [4, 12]. Because LPS is vital for the structural integrity and antibiotic resistance of Gram-negative bacteria, the LptB2FGC complex is a high-priority target for novel antimicrobial agents [2, 8]. Drugs like zosurabalpin (RG6006) specifically inhibit this complex, leading to the accumulation of LPS in the inner membrane and subsequent bacterial cell death [2]. This target is particularly relevant for treating multidrug-resistant infections, such as those caused by carbapenem-resistant Acinetobacter baumannii [2]. The complex also exhibits regulatory mechanisms where the LptC transmembrane helix modulates ATPase activity to ensure efficient transport [13, 11].

Other names

LptB2FG-LptC complexLptB2FG-C complexLPS transport unitInner membrane lipopolysaccharide transport complexLptB2FGC complex

Inhibition of the LptB2FGC complex, which blocks the transport of lipopolysaccharide from the inner membrane to the outer membrane, leading to bacterial cell death.