Multidrug resistance protein (Mdr)-alkaline phosphatase hybrids in Escherichia coli suggest a major revision in the topology of the C-terminal half of Mdr.
Recent studies reveal that the organization of the multidrug resistance protein (Mdr) in the membrane is probably not exactly as predicted from hydropathy profiling. When expressed in Escherichia coli, phoA gene fusions can be utilized to study the membrane topology of Mdr. Using this approach, it was proposed recently that the N-terminal hydrophobic domain of Mdr spans the membrane six times, in a different fashion from that predicted by hydropathy analysis (Bibi, E. and Béjà, O. (1994) J. Biol. Chem. 269, 19910-19915). In this study, we analyze mdr-phoA fusions constructed in the C-terminal half of Mdr. Overall, the results presented here lead to a significant revision in the membrane topology model of the C-terminal half of Mdr. The new topology is discussed with regard to the hydropathy profiles of the well characterized ABC proteins MalG and MalF, which are strikingly similar to those of the N- and C-terminal halves of Mdr, respectively.
Béjà
O
O
Department of Biochemistry, Weizmann Institute of Science, Rehovot, Israel.
Bibi
E
E
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry* / Q000235:genetics; D018528:ATP-Binding Cassette Transporters; D000469:Alkaline Phosphatase / Q000737:chemistry / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry; D002352:Carrier Proteins / Q000737:chemistry; D018432:Drug Resistance, Multiple; D004926:Escherichia coli / Q000235:genetics; D029968:Escherichia coli Proteins; D058619:Maltose-Binding Proteins; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins; D017433:Protein Structure, Secondary; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D002352:Carrier Proteins; D029968:Escherichia coli Proteins; C079123:MalG protein, E coli; D058619:Maltose-Binding Proteins; D009004:Monosaccharide Transport Proteins; D011993:Recombinant Fusion Proteins; C461599:maltose transport system, E coli; D000469:Alkaline Phosphatase