Abstract
Highlights
- Flucs are highly selective fluoride channels that protect microbes against cytoplasmic accumulation of toxic fluoride ion.
- Flucs are found as dual-topology homodimers, heterodimers, and fused 2-domain proteins with inverted topologies.
- Crystal structures of dual-topology Flucs show a symmetrical protein with two pores and a buried Na+ ion at the dimer interface.
- Both pores function in the homodimers, but in heterodimers and 2-domain fused proteins, the second pore has degraded.
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.
Graphical abstract
- Flucs are highly selective fluoride channels that protect microbes against cytoplasmic accumulation of toxic fluoride ion.
- Flucs are found as dual-topology homodimers, heterodimers, and fused 2-domain proteins with inverted topologies.
- Crystal structures of dual-topology Flucs show a symmetrical protein with two pores and a buried Na+ ion at the dimer interface.
- Both pores function in the homodimers, but in heterodimers and 2-domain fused proteins, the second pore has degraded.
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.
Graphical abstract
