9OP1

Cryo-EM structure of Candida albicans fluoride channel FEX in complex with Fab fragment

Summary for 9OP1

• Entry DOI: 10.2210/pdb9op1/pdb
• EMDB information: 70677
• Descriptor: 10E8v4 Fab Heavy Chian, 10E8v4 Fab Light Chain, Transmembrane protein gp41,Fluoride export protein 1 (3 entities in total)
• Functional Keywords: fluoride channel, fluoride exporter, fex, membrane protein
• Biological source: Homo sapiens; More
• Total number of polymer chains: 3
• Total formula weight: 86320.12

Authors

Kang, C.-Y.,An, M.J.,Ohi, M.D.,Stockbridge, R.B. (deposition date: 2025-05-16, release date: 2025-12-03, Last modification date: 2025-12-24)

Primary citation

Kang, C.Y.,An, M.,Heidari, S.,Torabifard, H.,Ohi, M.D.,Stockbridge, R.B.
The molecular mechanism of fluoride export by the eukaryotic fluoride channel FEX.
Nat Commun, 2025

PubMed Abstract: Much of life on Earth, including plants, fungi, and bacteria, evolved to resist toxic environmental fluoride. In eukaryotes, the major resistance mechanism is fluoride export by membrane proteins known as FEX. Using electrophysiology and transport assays, we establish that FEX from plants and yeasts are highly selective fluoride channels. Fluoride transport activity depends on reversible sodium ion binding, but sodium itself is not transported. We determine a structure of a FEX protein, from pathogenic yeast Candida albicans, using cryo-EM. Bolstered by mutagenesis studies, this structure reveals a fluoride permeation route through a single phenylalanine-lined pore. Molecular dynamics simulations demonstrate that a cation binding motif adjacent to the pore provides a stable sodium binding site that is accessible from the external aqueous solution. Comparison to the structurally related bacterial fluoride channels, Flucs, provides a glimpse of the evolution of structural and mechanistic complexity in a membrane protein family with inverted repeat architecture.

PubMed: 41381451
DOI: 10.1038/s41467-025-67289-0

Experimental method

ELECTRON MICROSCOPY (4.05 Å)