[1][2] The major facilitator superfamily (MFS) are membrane proteins which are expressed ubiquitously in all kingdoms of life for the import or export of target substrates.

The two halves of the protein pack against each other in a clam-shell fashion, sealing via interactions at the ends of the transmembrane helices and extracellular loops.

[7][8] This forms a large aqueous cavity at the center of the membrane, which is alternatively open to the cytoplasm or periplasm/extracellular space.

[9][10] Many MFS transporters are thought to be dimers through in vitro and in vivo methods, with some evidence to suggest a functional role for this oligomerization.

For example, in the best studied MFS transporter, LacY, lactose and protons typically bind from the periplasm to specific sites within the aqueous cleft.

This drives closure of the extracellular face, and opening of the cytoplasmic side, allowing substrate into the cell.

[17] Other MFS transporters are notable for a lack of selectivity, extruding broad classes of drugs and xenobiotics.

[9][10] While one substrate of particular biological importance is often used to name the transporter or family, there may also be co-transported or leaked ions or molecules.

Evidence suggests that the MFS permeases arose by a tandem intragenic duplication event in the early prokaryotes.