The major facilitator superfamily (MFS) revisited

Abstract

The major facilitator superfamily (MFS) is the largest known superfamily of secondary carriers found in the biosphere. It is ubiquitously distributed throughout virtually all currently recognized organismal phyla. This superfamily currently (2012) consists of 74 families, each of which is usually concerned with the transport of a certain type of substrate. Many of these families, defined phylogenetically, do not include even a single member that is functionally characterized. In this article, we probe the evolutionary origins of these transporters, providing evidence that they arose from a single 2‐transmembrane segment (TMS) hairpin structure that triplicated to give a 6‐TMS unit that duplicated to a 12‐TMS protein, the most frequent topological type of these permeases. We globally examine MFS protein topologies, focusing on exceptional proteins that deviate from the norm. Nine distantly related families appear to have members with 14 TMSs in which the extra two are usually centrally localized between the two 6‐TMS repeat units. They probably have arisen by intragenic duplication of an adjacent hairpin. This alternative topology probably arose multiple times during MFS evolution. Convincing evidence for MFS permeases with fewer than 12 TMSs was not forthcoming, leading to the suggestion that all 12 TMSs are required for optimal function. Some homologs appear to have 13, 14, 15 or 16 TMSs, and the probable locations of the extra TMSs were identified. A few MFS permeases are fused to other functional domains or are fully duplicated to give 24‐TMS proteins with dual functions. Finally, the MFS families with no known function were subjected to genomic context analyses leading to functional predictions.

Relative Domain Folding and Stability of a Membrane Transport Protein

“…Insertion of the second, C domain of LacY does not appear to require the equivalent regions of the domain at the initial helix of the C domain to have enhanced stability. This is despite the fact 13 that that the C domain can be expressed and folded in the absence of the N domain 32 , and that the two domains exhibit pseudo symmetry and are thought to arise from gene duplication 33 .…”

A link between host plant adaptation and pesticide resistance in the polyphagous spider mite Tetranychus urticae

“…Multiple MFS family members were differentially regulated in both Tomato-5G and resistant strains. MFS transporters are single-polypeptide carriers that work in symport/antiport (79,80), and studies in bacteria and fungi have identified roles in the transport of toxic substances (81)(82)(83). For example, overexpression of the mfsM2 gene in a sensitive strain of Botrytis cinerea, a fungal plant pathogen, led to drug-resistance levels similar to those of a fungicide-resistant B. cinerea strain (82).…”

NRT2.4 and NRT2.5 Are Two Half-Size Transporters from the Chlamydomonas NRT2 Family

“…The 12 transmembrane helixes are the most frequent topology of MFS transporters and believed to be the result of an ancient gene duplication of a gene encoding a single domain with six transmembrane helixes. The maintenance of both domains in a single polypeptide chain could perhaps have been favored during evolution in order to facilitate substrate recognition and conformational changes during the transport [25]. It has been reported that halves of sucrose transporters StSUT1 from Solanum tuberosum show intermolecular interactions and reconstitute sucrose transport activity similar to the intact protein [46].…”