The multidrug transporters--proteins of an ancient immune system.
The multidrug resistance proteins, discovered as membrane transporters producing chemotherapy-resistance in cancer, are functioning as complex cellular defence systems through recognition and energy-dependent removal of a large variety of toxic agents. The multidrug transporters belong to the ATP-binding cassette (ABC) transporters, present both in prokaryotes and eukaryotes and built from a combination of characteristic membrane-spanning helices and cytoplasmic ATP-binding domains. In mammals the MDR1 (P-glycoprotein) extrudes large hydrophobic compounds and provides the basis of the blood-brain and the blood-testis barrier for such molecules. The multidrug resistance-associated protein (MRP) and its homologues have a major role in the cellular export of large organic anions, including e.g. conjugated bile salts and glutathione-conjugates. The substrate recognition, that is the self and non-self discrimination and the ATP-dependent foreign agent extrusion are directly coupled within the structure of these large plasma membrane proteins. Here we suggest that the multidrug transporters are essential parts of our immune-defence system, working as 'cellular antitoxic' mechanisms.
Sarkadi
B
B
National Institute of Haematology and Immunology, Membrane Research and Immunopathology Group of the Hungarian Academy of Sciences, Budapest.
Müller
M
M
Holló
Z
Z
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000276:immunology; D018528:ATP-Binding Cassette Transporters / Q000276:immunology; D000818:Animals; D018407:Bacterial Physiological Phenomena; D002352:Carrier Proteins / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D011487:Protein Conformation
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D002352:Carrier Proteins