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

FEBS Lett. 2003 Nov 27;555(1):96-101. doi: 10.1016/s0014-5793(03)01087-1.


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 A. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Binding Sites
  • Biological Transport, Active
  • Carbohydrate Metabolism
  • Escherichia coli / metabolism*
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / metabolism*
  • Membrane Transport Proteins / chemistry*
  • Membrane Transport Proteins / metabolism*
  • Models, Molecular
  • Monosaccharide Transport Proteins*
  • Protein Conformation
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Static Electricity
  • Symporters*
  • Thermodynamics


  • Escherichia coli Proteins
  • LacY protein, E coli
  • Membrane Transport Proteins
  • Monosaccharide Transport Proteins
  • Symporters
  • lactose permease