Transporters can be grouped in two classes, primary and secondary carriers.
The primary active transporters drive solute accumulation or extrusion by
using ATP hydrolysis, photon absorption, electron flow, substrate
decarboxylation or methyl transfer. If charged molecules are unidirectionally
pumped as a consequence of the consumption of a primary cellular energy
source, electron chemical potential results. This potential can than be used
to drive the active transport of additional solutes via secondary carriers.
Among the different transporter the two largest families that occur
ubiquitously in all classifications of organisms are the ATP-Binding Cassette
(ABC) primary transporter superfamily and the Major
Facilitator Superfamily (MFS). The MFS transporters are single-polypeptide
secondary carriers capable only of transporting small solutes in response to
chemiosmotic ion gradients
[2][4]. They function as uniporters, symporters or
antiporters. In addition their solute specificity are also diverse. MFS
proteins contain 12 transmembrane regions (with some variations).
The 3D-structure of human GLUT1, an archetype of the major facilitator
superfamily has been solved
[1]. Helices 1-5, 8, 10-12 are
arranged in a 9-member barrel-like manner, delimiting a hydrophilic central
channel. Helix 7 is located in the center of the channel suggesting a role in
regulating transport of solutes through the channel.
Some proteins known to belong to the MFS superfamily are listed below:
- Sugar transporters. The largest family, they can function by uniport,
solute-solute antiport or solute-cation symport depending on the system or
conditions.
- Drug:H+ antiporters or multidrug transporters. The extrusion of cytotoxic
drugs from multidrug resistant cells by overexpressed multidrug transporter
is an important cause of failure of the drug-based treatment of patient
with cancers or infections by pathogenic microorganisms [4].
- Organophosphate:Pi antiporters (OPA). Small permeases restricted to
bacteria.
- Oligosaccharide:H+ symporters (OHS). Permeases restricted to bacteria.
- Metabolite:H+ symporters (MHS).
- Nitrate/nitrite symporter (NNP). This family is present in bacteria, fungi
and plants. It catalyzes either nitrate uptake or nitrite efflux.
- Phosphate:H+ symporters (PHS). It is present only in fungi and plants.
- Nucleoside:H+ symporters (NHS). Small permeases restricted to Gram-negative
bacteria.
- Oxalate/formate antiporters (OFA). Present in bacteria, archaea and
eukaryotes.
- Sialate:H+ symporters (SHS). Small permeases restricted to Gram-negative
bacteria.
- Monocarboxylate porters (MCP).
- Anion:cation symporters (ACS).
- Aromatic acid:H+ symporters (AAHS). They transport a variety of aromatic
acids as well as cis,cis-muconate. One member of this family (PCAK) serves
as a chemoreceptor allowing the bacteria to swim up concentration gradiants
of its substrate
[3].
- Cyanate permeases (CP). Small bacterial proteins of around 400 residues.
- Proton-dependent oligopeptide transporters (POT). AAHS and POT are the most
divergent MFS families.
The profile we developed covers the 12 transmembrane regions.