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Research article2008Peer reviewedOpen access

Salt-bridge dynamics control substrate-induced conformational change in the membrane transporter GlpT

Law, Christopher J.; Almqvist, Jonas; Bernstein, Adam; Goetz, Regina M.; Huang, Yafei; Soudant, Celine; Laaksonen, Aatto; Hovmoller, Sven; Wang, Da-Neng


Active transport of substrates across cytoplasmic membranes is of great physiological, medical and pharmaceutical importance. The glycerol-3-phosphate (G3P) transporter (GlpT) of the E. coli inner membrane is a secondary active antiporter from the ubiquitous major facilitator superfamily that couples the import of G3P? to the efflux of inorganic phosphate (Pi) down its concentration gradient. Integrating information from a novel combination of structural, molecular dynamics simulations and biochemical studies, we identify the residues involved directly in binding of substrate to the inward-facing conformation of GlpT, thus defining the structural basis for the substrate-specificity of this transporter. The substrate binding mechanism involves protonation of a histidine residue at the binding site. Furthermore, our data suggest that the formation and breaking of inter- and intradomain salt bridges control the conformational change of the transporter that accompanies substrate translocation across the membrane. The mechanism we propose may be a paradigm for organophosphate:phosphate antiporters. (c) 2008 Elsevier Ltd. All rights reserved.


antiporter; membrane transport; major facilitator superfamily; molecular dynamics simulations; secondary active transport

Published in

Journal of Molecular Biology
2008, Volume: 378, number: 4, pages: 828-839

      SLU Authors

    • Huang Almqvist, Yafei

      • Department of Molecular Biology, Swedish University of Agricultural Sciences

    UKÄ Subject classification

    Biochemistry and Molecular Biology

    Publication identifier


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