13.8: ABC Transporters: Exporter
ATP-binding cassette or ABC transporter is the largest superfamily of integral membrane proteins. The transporters have transmembrane-binding domains (TMDs) and nucleotide-binding domains (NBDs). The TMDs are specific to their substrates, whereas the NBDs are similar to engines that complete ATP hydrolysis to complete the substrate transport. They can be full transporters consisting of two TMDs and NBDs, half transporters with one TMD and NBD, while some encoded with a single TMD or NBD are single-domain structures.
The eukaryotic ABC transporters can only function as exporters of solute. Except for some plants, bacteria have both ABC importers and exporters.
There are 49 known ABC genes in humans, classified into seven families. The ATP-binding cassette sub-family B member 1 (ABCB1) or P-glycoprotein 1 is responsible for transporting various natural and metabolic toxins out of the cells. However, during its evolution, ABCB1 acquired the ability to transport drugs whose structures are similar to those of endogenous toxins, thus becoming a significant cause of drug resistance. This is a massive concern while treating cancer, as it prevents intracellular accumulation of anti-cancer drugs and reduces treatment efficacy.
In a related example, Plasmodium falciparum, a unicellular eukaryote that causes malaria, is commonly treated with chloroquine. However, over time, it has developed resistance to chloroquine due to mutations in the Plasmodium falciparum multidrug resistance protein 1 (PfMDR1) transporter that helps reduce intracellular drug concentration.
