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

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

Research output: Contribution to journalArticlepeer-review

44 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)828-839
Number of pages12
JournalJournal of Molecular Biology
Volume378
Issue number4
DOIs
Publication statusPublished - 09 May 2008

ASJC Scopus subject areas

  • Virology

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