ATP-DEPENDENT TRANSPORT SYSTEMS IN BACTERIA AND HUMANS: Relevance to Cystic Fibrosis and Multidrug Resistance

Abstract

The prokaryotic permeases are members of a superfamily of membrane transporters called traffic ATPases, which includes the medically important eukaryotic multidrug resistance (MDR) protein and cystic fibrosis transmembrane regulator (CFTR). Members of this superfamily have extensive sequence and structural similarity, in particular in an ATP-binding motif, and are believed to use ATP to energize translocation of substrates across biological membranes. The prokaryotic histidine permease is well-characterized and serves as a convenient model system. In this review, we highlight some of the biochemical and molecular biological approaches used to study the functional and architectural organization of this permease and relate the results of these approaches to what is known about other traffic ATPases. We have identified specific regions that we believe critical for the function of the histidine permease and propose that the corresponding regions in the eukaryotic traffic ATPases are also important for their function. In light of the fact that CFTR (and possibly the MDR protein) is an ion channel, we compare the properties of channels and transporters; in addition, we discuss the possibility that other members of the traffic ATPases may also have channel-like activity.

Characterization of the Adenosine Triphosphatase Activity of the Periplasmic Histidine Permease, a Traffic ATPase (ABC Transporter)

“…Effect of NaCl, MgSO 4 , and pH-NaCl is not required for activity and at concentrations higher than 100 mM it inhibits activity, with 50% inhibition at 200 mM NaCl (Fig. 6A).…”

“…The superfamily includes bacterial periplasmic permeases, the yeast STE6 gene product, the mammalian P-glycoprotein (multidrug resistance protein or MDR), 1 the human cystic fibrosis transmembrane conductance regulator (CFTR), and the mammalian heterodimeric transporter (TAP1/TAP2) involved in antigen processing (3,4). The periplasmic histidine permease in Salmonella typhimurium and the maltose permease in Escherichia coli have been extensively characterized; both are good model systems for this superfamily (5)(6)(7).…”

UV irradiation inhibits ABC transporters via generation of ADP-ribose by concerted action of poly(ADP-ribose) polymerase-1 and glycohydrolase

“…3 The substrate spectra and the inhibitor profiles of ABC transporters markedly overlap. 5 ABC transporters play a role in the maintenance of membrane lipid bilayer and in the transport of fatty acids and steroids. 3 It has been suggested that the ABC transporter ABCA1 induces modifications in lipid distribution of plasma membrane, evidenced by exofacial flopping of phosphatidylserine.…”

Heat shock induction by a misassembled cytoplasmic membrane protein complex in Escherichia coli

“…This complex is composed of two hydrophobic proteins, MalF and MalG, and two copies of a cytoplasmic ATP-binding protein, MalK, forming the MalFGK2 complex (Davidson and Nikaido, 1990;. The system belongs to the superfamily of ATP-binding cassette (ABC) transporters (Nikaido, 1994), which share the same structural organization (for reviews, see Higgins, 1992;Doige and Ames, 1993). We report here that the overproduction of protein MalF in the absence of its membrane partners specifically induces the expression of the phtrA 24 -dependent promoter.…”