β-Galactoside Transport in Escherichia Coli: The Ins and Outs of Lactose Permease

Abstract

Accumulation of β-galactosides against a concentration gradient in Escherichia coli is carried out by the lactose (lac) permease, a hydrophobic polytopic cytoplasmic membrane protein that catalyzes the coupled translocation of β-galactosides and H⁺ with a stoichiometry of unity (i.e. β-galactoside/H⁺ symport or cotransport) (cf. Kaback, 1983, 1986, 1990 for reviews). Under physiological conditions, where the H⁺ electrochemical gradient across the cytoplasmic membrane (Δμ̄_H ⁺)¹ is interior negative and/or alkaline, lac permease utilizes free energy released from downhill translocation of H⁺ to drive accumulation of β-galactosides against a concentration gradient. In the absence of Δμ̄_H ⁺, the permease catalyzes the converse reaction, utilizing free energy from downhill translocation of β-galactosides to drive uphill translocation of H⁺ and generating Δμ̄_H ⁺, the polarity of which depends upon the direction of the substrate concentration gradient. As such, lac permease is a paradigm for a wide variety of biological machines in both prokaryotic and eukaryotic membranes that transduce the free energy of an electrochemical ion gradient into work or into other forms of chemical energy (i.e., ATP).