A topologically diverse family of fluoride channels

Dual-topology proteins are likely evolutionary antecedents to a common motif in membrane protein structures, the inverted repeat. A family of fluoride channels, the Flucs, which protect microorganisms, fungi, and plants against cytoplasmic fluoride accumulation, has representatives of all topologies along this evolutionary trajectory, including dual-topology homodimers, antiparallel heterodimers, and, in eukaryotes, fused two-domain proteins with an inverted repeat motif. Recent high-resolution crystal structures of dual-topology homodimers, coupled with extensive functional information about both the homodimers and two-domain Flucs, provide a case study of the co-evolution of fold and function.