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 resistanc e protein (Mdr) in the membrane is probably not exactly as predicted f rom hydropathy profiling, When expressed in Escherichia coli, phoA gen e fusions can be utilized to study the membrane topology of Mdr. Using this approach, it was proposed recently that the N-terminal hydrophob ic domain of Mdr spans the membrane six times, in a different fashion from that predicted by hydropathy analysis (Bibi, E. and Beja, O. (199 4) J. Biol. Chem. 269, 19910-19915). In this study, we analyze mdr-pho A fusions constructed in the C-terminal half of Mdr. Overall, the resu lts presented here lead to a significant revision in the membrane topo logy model of the C-terminal half of Mdr. The new topology is discusse d 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.