The lactose permease of Escherichia coli: overall structure, the sugar‐binding site and the alternating access model for transport

Abstract

Membrane transport proteins transduce free energy stored in electrochemical ion gradients into a concentration gradient and are a major class of membrane proteins, many of which play important roles in human health and disease. Recently, the X‐ray structure of the Escherichia coli lactose permease (LacY), an intensively studied member of a large group of related membrane transport proteins, was solved at 3.5 Å. LacY is composed of N‐ and C‐terminal domains, each with six transmembrane helices, symmetrically positioned within the molecule. The structure represents the inward‐facing conformation, as evidenced by a large internal hydrophilic cavity open to the cytoplasmic side. The structure with a bound lactose homolog reveals the sugar‐binding site in the cavity, and a mechanism for translocation across the membrane is proposed in which the sugar‐binding site has alternating accessibility to either side of the membrane.