Abstract
The formate/nitrite transporter (FNT) family of integral membrane proteins comprises pentameric channels for monovalent anions that exhibit a broad specificity for small anions such as chloride, the physiological cargo molecules formate, nitrite, and hydrosulfide, and also larger organic acids. Three-dimensional structures are available for the three known subtypes, FocA, NirC, and HSC, which reveal remarkable evolutionary optimizations for the respective physiological context of the channels. FNT channels share a conserved translocation pathway in each protomer, with a central hydrophobic cavity that is separated from both sides of the membrane by a narrow constriction. A single protonable residue, a histidine, plays a key role by transiently protonating the transported anion to allow an uncharged species to pass the hydrophobic barrier. Further selectivity is reached through variations in the electrostatic surface potential of the proteins, priming the formate channel FocA for anion export, whereas NirC and HSC should work bidirectionally. Electrophysiological studies have shown that a broad variety of monovalent anions can be transported, and in the case of FocA, these match exactly the products of mixed-acid fermentation, the predominant metabolic pathway for most enterobacterial species.
The authors thank the staff at beam lines X06DA and X06SA at the Swiss Light Source, Villigen, Switzerland, for their continuous support during data collection and Elke Gerbig-Smentek for the excellent technical assistance. This work was supported by Deutsche Forschungsgemeinschaft [grants An 676/1 and An 676/3 to S.L.A.A., grants Ei 520/3 and Ei 520/6 (RU 929) to O.E., and IRTG 1478].
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