Lactose Permease: From Membrane to Molecule to Mechanism

  • Lan Guan
  • H. Ronald Kaback
Reference work entry
Part of the Handbook of Hydrocarbon and Lipid Microbiology book series (HHLM)


Lactose permease of Escherichia coli (LacY), a galactoside/H+ symporter, is a paradigm for cation-coupled membrane-transport proteins. This integral membrane protein is composed of two pseudo-symmetrical six-helix bundles surrounding an internal hydrophilic cavity with binding sites for sugar and H+ at the apex of the molecule in the approximate middle of the membrane. These structural features allow LacY to utilize an alternating-access mechanism to catalyze sugar/H+ symport in either direction across the cytoplasmic membrane. The H+-binding site is occupied under most physiological conditions because of a markedly perturbed pKa, and galactoside binding causes transition of the ternary complex to an occluded intermediate that then opens to alternative sides of the membrane. Binding and alternating access of the binding sites to either side of the membrane occur independently of the electrochemical H+ gradient (\( \Delta {\overset{\sim }{\mu}}_{{\mathrm{H}}^{+}}\Big).\, \)However, in the absence of \( \Delta {\overset{\sim }{\mu}}_{{\mathrm{H}}^{+}},\, \)deprotonation is rate limiting, while in the presence of \( \Delta {\overset{\sim }{\mu}}_{{\mathrm{H}}^{+}} \) (interior negative and/or alkaline), deprotonation is no longer rate limiting because there is a driving force on the H+. Although the dissociation constant (Kd) value for galactoside remains constant on either side of the membrane, Km decreases 50- to 100-fold, and by this means accumulation against a sugar concentration gradient is achieved.


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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Cell Physiology and Molecular Biophysics, Center for Membrane Protein ResearchTexas Tech University Health Sciences CenterLubbockUSA
  2. 2.Departments of Physiology, Microbiology, Immunology and Molecular Genetics, Molecular Biology InstituteUniversity of CaliforniaLos AngelesUSA

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