Topology of P-glycoprotein as determined by epitope mapping of MRK-16 monoclonal antibody

摘要: There is growing evidence for the direct role of P-glycoprotein mediating multidrug resistance in tumor cells. thought to function as an energy-dependent drug efflux pump. The monoclonal antibody MRK-16 binds external domain and partially inhibits multidrug-resistant As approach toward elucidating mechanism by which affects transport, we undertook definition precise binding site this antibody. In study have mapped epitope a resolution single amino acid using series overlapping synthetic peptides. We demonstrate that recognizes only class I isoform (MDR1) human its encompasses at least two (first fourth) six predicted extracellular peptide loops. These results suggest discontinuous sequences involved are separated about 625 acids linear sequence must be spatially situated close proximity native protein. Based on these results, present model transmembrane alpha-helical packing lipid bilayer. This may implications understanding transport.