ABC transporters

ATP-binding cassette transporters (ABC transporters) are members of a transport system superfamily that is one of the largest and is possibly one of the oldest families with representatives in all extant phyla from prokaryotes to humans. ABC transporter often consist of multiple subunits, one or two of which are transmembrane proteins and one or two of which are membrane-associated ATPases. The ATPase subunits that utilize the energy of adenosine triphosphate (ATP) binding and hydrolysis to energize the translocation of various substrates across membranes, either for uptake or for export of the substrate. Most but not all uptake systems also have an extracytoplasmic receptor, a solute binding protein. Some homologous ATPases function in non-transport-related processes such as translation of RNA and DNA repair. ABC transporters are considered to be with the ABC superfamily based on the sequence and organization of their ATP-binding cassette (ABC) domains, even though the integral membrane proteins may have evolved independently several times, and thus comprise different protein families. The integral membrane proteins of ABC exporters appear to have evolved independently at least three times. ABC1 exporters evolved by intragenic triplication of a 2 TMS precursor to give 6 TMS proteins. ABC2 exporters evolved by intragenic duplication of a 3 TMS precursor, and ABC3 exporters evolved from a 4 TMS precursor which duplicated either extragenicly to give two 4 TMS proteins, both required for transport function, or intragenicly to give 8 or 10 TMS proteins. The 10 TMS proteins appear to have two extra TMSs between the two 4 TMS repeat units. Similarly, it is possible that the integral membrane proteins of ABC uptake systems evolved at least 3 times independently, based on their high resolution 3-dimensional structures. ABC uptake porters take up a large variety of nutrients, biosynthetic precursors, trace metals and vitamins, while exporters transport lipids, sterols, drugs, and a large variety of primary and secondary metabolites. Some of these exporters in humans are involved in tumor resistance, cystic fibrosis and a range of other inherited human diseases. High level expression of the genes encoding some of these exporters in both prokaryotic and eukaryotic organisms (including human) result in the development of resistance to multiple drugs such as antibiotics and anti-cancer agents.