Transport of solutes across membranes is carried out by specific transport proteins which alternately expose the substrate binding-site to either side of the membrane. X-ray crystallographic data for several secondary transporters from diverse families support this concept and intriguingly, reveal the presence of internal structural repeats with inverted transmembrane topologies. In my talk I will describe work in which we have shown, using computational modelling of four different secondary transporter families, that these structural repeats can encode two degenerate conformations of the same protein. These results demonstrate the general role of inverted-topology repeats ­ and of pseudo-symmetry ­ in the alternating-access mechanism of secondary transport."