GnFE

GnFE is a bacterial protein that participates in the regulation of metal ion homeostasis, particularly nickel and cobalt. The gnfe gene is typically located within the gnfe-gnfD operon found in many Gram‑negative species such as Pseudomonas aeruginosa and several Proteobacteria. Transcription of the operon is induced under metal‑limited conditions.

The GnFE protein is predicted to be a periplasmic protein containing an N‑terminal signal peptide that directs it to the periplasmic space. The mature protein comprises a single α/β domain that shares similarity with disulfide‑bond formation enzymes (DsbA/DsbB family) and contains a conserved CXXC motif that is believed to bind divalent cations. Crystal structures of homologues in related bacteria have revealed a compact fold with a shallow metal‑binding pocket.

Functionally, GnFE interacts with the membrane‑associated transcriptional regulator GnfD. Together they form a two‑component regulatory system that controls the expression of genes in the gnf operon. When metal ions are scarce, GnFE binds the regulator and induces a conformational change that releases DNA, promoting transcription of metal‑transport systems. Mutational analysis shows that deletion of gnfe leads to increased sensitivity to nickel and cobalt salts, whereas over‑expression confers growth advantage in metal‑chelated media.

Evolutionary analyses indicate that GnFE homologs are widespread among bacteria possessing metal‑transport regulons, but are absent in Gram‑positive species, reflecting divergent metal‑homeostasis strategies. Although its exact catalytic activity remains unconfirmed, biochemical assays suggest that GnFE may function as a metallochaperone rather than a catalytic enzyme.

Research on GnFE has implications for biotechnology, particularly in the design of bacteria capable of bio‑remediation of heavy‑metal pollutants. Ongoing structural and functional studies aim to clarify its role in metal‑ion sensing and its potential as a target for antibacterial strategies.