The twisted relation between Pnu and SWEET transporters

• SWEET and Pnu transporters have similar structures but lack sequence similarity.
• A topological difference also raises questions about their evolutionary relatedness.
• A 3D domain swap can explain the topological differences.
• We propose a pathway by which the SWEET and Pnu transporters may have diverged.

The evolutionary relation between sugar and vitamin transporters from the SWEET and Pnu families is unclear. They have similar 3D structures, but differ in the topology of their secondary structure elements, and lack significant sequence similarity. Here we analyze the structures and sequences of different members of the SWEET and Pnu transporter families and propose an evolutionary pathway by which they may have diverged from a common ancestor. A 3D domain swapping event can explain the topological differences between the families, as well as the puzzling observation that a highly conserved and essential sequence motif of the SWEET family (the PQ loop) is absent from the Pnu transporters.