Salt-bridge dynamics control substrate-induced conformational change in the membrane transporter GlpT
2008 (English)In: Journal of Molecular Biology, ISSN 0022-2836, E-ISSN 1089-8638, Vol. 378, no 4, 828-839 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2008. Vol. 378, no 4, 828-839 p.
antiporter; membrane transport; major facilitator superfamily; molecular dynamics simulations; secondary active transport
Biochemistry and Molecular Biology
IdentifiersURN: urn:nbn:se:su:diva-24727DOI: 10.1016/j.jmb.2008.03.029ISI: 000256180100006OAI: oai:DiVA.org:su-24727DiVA: diva2:198199