The multidrug transporters--proteins of an ancient immune system

Immunol Lett. 1996 Dec;54(2-3):215-9. doi: 10.1016/s0165-2478(96)02676-4.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / immunology
  • ATP-Binding Cassette Transporters / immunology
  • Animals
  • Bacterial Physiological Phenomena
  • Carrier Proteins / immunology*
  • Humans
  • Immunity, Cellular
  • Protein Conformation

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP-Binding Cassette Transporters
  • Carrier Proteins