Tüting, C., Janson, K., Kammel, M., Ihling, C., Lorenz, J., Kyrilis, F. L., Hamdi, F., Erdmann, C., Sinz, A., Sawers, R. G., & Kastritis, P. L.
Conserved hydrophilic checkpoints tune FocA-mediated formate:H+ symport. Nature Communications, 16(1), 9476. https://doi.org/10.1038/s41467-025-65159-3
Published: 27 October 2025
Abstract: FocA belongs to the widespread, evolutionarily ancient formate-nitrite transporter (FNT) family of pentameric anion channels and translocates formic acid bidirectionally. Here, we identify compartmentalized polarity distribution across the complete FocA pore structure – resolved at 2.56 Å – mirrored against a two-fold axis with H209 at its center. A FocA-H209N variant that exhibits an efflux-only channel-like function in vivo reveals a density consistent with formate located directly at N209, abolishing the channel’s amphiphilicity. Pyruvate formate-lyase, which generates formate, orients at the cytoplasmic face where formate delivery is regulated by conformational changes in the FocA vestibule. Comparisons with other FNTs suggest a tuning mechanism of formate-specific transport via checkpoints enriched in hydrophilic residues.
© 2025 The Author(s). Published by Springer Nature. This is an open access article under the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).