Structure of the formate transporter FocA reveals a pentameric aquaporin-like channel

Abstract

FocA is a representative member of the formate-nitrite transporter family, which transports short-chain acids in bacteria, archaea, fungi, algae and parasites. The structure and transport mechanism of the formate-nitrite transporter family remain unknown. Here we report the crystal structure of Escherichia coli FocA at 2.25 A resolution. FocA forms a symmetric pentamer, with each protomer consisting of six transmembrane segments. Despite a lack of sequence homology, the overall structure of the FocA protomer closely resembles that of aquaporin and strongly argues that FocA is a channel, rather than a transporter. Structural analysis identifies potentially important channel residues, defines the channel path and reveals two constriction sites. Unlike aquaporin, FocA is impermeable to water but allows the passage of formate. A structural and biochemical investigation provides mechanistic insights into the channel activity of FocA.

Identity of a Plasmodium lactate/H+ symporter structurally unrelated to human transporters

“…PFC0725c encodes a single putative formate-nitrite transporter (PfFNT, 34.4 kDa) whose expression profile 11,12 parallels that of the plasmodial HT (Fig. 1b), the lactate dehydrogenase and all glycolytic enzymes ( Supplementary Fig.…”

“…We used the available crystal data of various bacterial FNTs 12,[14][15][16] ( Supplementary Fig. 5).…”

“…4 and Supplementary Table 2). Generally, FNTs are restricted to microorganisms and operate as pentameric, aquaporin-like transporters for formate [12][13][14] , nitrite 15 and hydrosulfide 16 . Yet, none of these anions have been reported to be relevant in plasmodial metabolism.…”

“…Deletion of the PfFNT gene, for which a conditional knockout system is likely to be required, will ultimately reveal its contribution to P. falciparum viability and virulence. It is particularly appealing that PfFNT is structurally unrelated to human transporters and that crystal data are available from homologous bacterial FNTs [12][13][14][15][16] , enabling development of lactate transport as a novel antimalarial drug target. Conversely, the identification of PfFNT inhibitors may aid development of antibiotics.…”

Aquaporins in sperm osmoadaptation: an emerging role for volume regulation

“…Indeed, recent fi ndings have demonstrated that a formate transporter shows an AQP-like channel structure [34,35] , thus lending support to the radical notion that an aquaporin structure may have the potential to function as a unidirectional water transporter in cooperation with other molecules, at least under certain circumstances.…”