Energy coupling in ABC exporters

Abstract

Multidrug transporters are important and interesting molecular machines that extrude a wide variety of cytotoxic drugs from target cells. This review summarizes novel insights in the energetics and mechanisms of bacterial ATP-binding cassette multidrug transporters as well as recent advances connecting multidrug transport to ion and lipid translocation processes in other membrane proteins.

The peptide sensor motif stabilizes the outward-facing conformation of TmrAB

“…Investigations into their allosteric relationship have focused on two motifs in each NBD, the Q-loop and X-loop [24][25][26] (Supplemental Figure 1). Both motifs are found on loops that bridge the NBDs to the TMDs and are highly conserved, with the X-loop found only in ABC exporters [27]. Mutations in the Q-loop of the drug transporter human P-glycoprotein (PgP) result in defects in the ability to transition to outward open and a decoupling of ATPase activity and substrate transport [28].…”

ABC systems: structural and functional variations on a common theme

“…The properties and the transport mechanism of such transporters are the subject of the review of Cédric Orelle and collaborators[11].Energy coupling of transport is very predominantly dependent on ATP binding and hydrolysis in ABC systems. However, Hendrik van Veen and collaborators provide arguments in favor of an involvement of ion-gradients in some members of this family, as discussed in their review[12].The emergence of multidrug resistant bacteria (MDR) and the decrease in the development of new antibiotics led to evaluation of the efficacy of new antibacterial agents. Bacterial antimicrobial peptides (bacteriocins) might be promising tools to combat drug resistance.…”