Major Facilitator Family

Major Facilitator Family

The Major Facilitator Superfamily (MFS) transporters are secondary carriers transporting small solutes in response to chemiosmotic ion gradients.

Recent genome-sequencing data and a wealth of biochemical and molecular genetics investigations have revealed the occurrence of dozens of families of primary and secondary transporters. Two such families have been found to occur ubiquitously in all classifications of living organisms. These are the ATP-binding cassette (ABC) superfamily and the major facilitator superfamily (MFS), also called the uniporter-symporter-antiporter family. While ABC family permeases are in general multicomponent primary active transporters, capable of transporting both small molecules and macromolecules in response to ATP hydrolysis the MFS transporters are single-polypeptide secondary carriers capable only of transporting small solutes in response to chemiosmotic ion gradients. Although well over 100 families of transporters have now been recognised and classified, the ABC superfamily and MFS account for nearly half of the solute transporters encoded within the genomes of microorganisms. They are also prevalent in higher organisms. The importance of these two families of transport systems to living organisms can therefore not be overestimated.

The MFS was originally believed to function primarily in the uptake of sugars but subsequent studies revealed that drug efflux systems, Krebs cycle metabolites, organophosphate:phosphate exchangers, oligosaccharide:H1 symport permeases, and bacterial aromatic acid permeases were all members of the MFS. These observations led to the probability that the MFS is far more widespread in nature and far more diverse in function than had been thought previously. 17 subgroups of the MFS have been identified.

Evidence suggests that the MFS permeases arose by a tandem intragenic duplication event in the early prokaryotes. This event generated a 2-transmembrane-spanner (TMS) protein topology from a primordial 6-TMS unit. Surprisingly, all currently recognised MFS permeases retain the two six-TMS units within a single polypeptide chain, although in 3 of the 17 MFS families, an additional two TMSs are found. Moreover, the well-conserved MFS specific motif between TMS2 and TMS3 and the related but less well conserved motif between TMS8 and TMS9 prove to be a characteristic of virtually all of the more than 300 MFS proteins identified.