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A Molecular Mechanism for Energy Coupling in a Membrane Transport Protein, the Lactose Permease of Escherichia coli
H. Ronald Kaback
Proceedings of the National Academy of Sciences of the United States of America
Vol. 94, No. 11 (May 27, 1997), pp. 5539-5543
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/42110
Page Count: 5
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A mechanism for the coupled translocation of substrate and H+ by the lactose permease of Escherichia coli is proposed, based on a variety of experimental observations. The permease is composed of 12 α -helical rods that traverse the membrane with the N and C termini on the cytoplasmic face. Four residues are irreplaceable with respect to coupling, and the residues are paired--Arg-302 (helix IX) with Glu-325 (helix X) and His-322 (helix X) with Glu-269 (helix VIII). In an adjacent region of the molecule at the interface between helices VIII and V is the substrate translocation pathway. Because of this arrangement, interfacial changes between helices VIII and V are transmitted to the interface between helices IX and X and vice versa. Upon ligand binding, a structural change at the interface between helices V and VIII disrupts the interaction between Glu-269 and His-322, Glu-269 displaces Glu-325 from Arg-302, and Glu-325 is protonated. Simultaneously, protonated Glu-325 becomes inaccessible to water, which drastically increases its pKa. In this configuration, the permease undergoes a freely reversible conformational change that corresponds to translocation of the ternary complex. To return to ground state after release of substrate, the Arg-302-Glu-325 interaction must be reestablished, which necessitates loss of H+ from Glu-325. The H+ is released into a water-filled crevice between helices IX and X which becomes transiently accessible to both sides of the membrane due to a change in helix tilt, where it is acted upon equally by either the membrane potential or the pH gradient across the membrane.
Proceedings of the National Academy of Sciences of the United States of America © 1997 National Academy of Sciences