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

JOURNAL OF MOLECULAR BIOLOGY

卷:378

Article

Law, Christopher J.^2,3  Almqvist, Jonas¹  Bernstein, Adam^2,3  Goetz, Regina M.^1,2,3  Huang, Yafei⁴  Soudant, Celine^2,3  Laaksonen, Aatto⁵  Hovmoller, Sven¹  Wang, Da-Neng^2,3 

[1] Stockholm Univ, Div Struct Chem, Arrhenius Lab, S-10691 Stockholm, Sweden

[2] NYU, Sch Med, Helen L & Martin S Kimmel Ctr Biol & Med, Skirball Inst Biomol Med, New York, NY 10016 USA

[3] NYU, Sch Med, Dept Cell Biol, New York, NY 10016 USA

[4] Swedish Univ Agr Sci, Dept Mol Biol, Uppsala Biomed Ctr, S-75324 Uppsala, Sweden

[5] Stockholm Univ, Arrhenius Lab, Div Phys Chem, S-10691 Stockholm, Sweden

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

DOI  :  10.1016/j.jmb.2008.03.029

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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