The mechanism of energy transduction in biological membranes is a fascinating unsolved problem in biology. It has been recognized for some time that the driving force for a variety of seemingly unrelated phenomena (e.g. secondary active transport, oxidative phosphorylation, rotation of the bacterial flagellar motor) is a bulk-phase, transmembrane electrochemical ion gradient. However, insight into the molecular mechanisms by which free energy stored in such gradients is transduced into work or into chemical energy is just beginning. Nonetheless, gene sequencing and analyses of deduced amino-acid sequences suggest that many biological machines involved in energy transduction, secondary transport proteins in particular (Henderson, 1990; Marger & Saier, 1993), fall into families encompassing proteins from archaea to the mammalian central nervous system, thereby raising the possibility that the members may have common basic structural features and mechanisms. In addition, many of these proteins play important roles in human disease (e.g. diabetes mellitus, glucose/galactose malabsorption, some forms of drug abuse, stroke, antibiotic resistance), as well as the mechanism of action of certain psychotropic drugs.

The focus of this review is on recent observations with a specific secondary transport protein, the lactose permease (lac permease) of Escherichia coli, as a representative of a huge number of proteins that catalyse similar reactions in virtually all biological membranes.