The mechanism of energy transduction in biological membranes is a fascinating
unsolved problem in biology. It has been recognized for some time that
driving force for a variety of seemingly unrelated phenomena (e.g. secondary
active transport, oxidative phosphorylation, rotation of the bacterial
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,
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
structural features and mechanisms. In addition, many of these proteins
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
virtually all biological membranes.