The lactose permease (LacY) of Escherichia coli is a paradigm
for the major facilitator superfamily (1) of membrane transport
proteins, many of which transduce free energy stored in an
electrochemical proton gradient into a concentration gradient of
substrate and vice versa (2). LacY contains 12 transmembrane
helices connected by hydrophilic loops with both the N and C
termini on the cytoplasmic face of the membrane (3–6), and it
is functionally and structurally a monomer (6–11).