Substrate-Na+ complex formation: Coupling mechanism for γ-aminobutyrate symporters

Anna Palló, Ágnes Simon, Ákos Bencsura, László Héja, Julianna Kardos

Research output: Contribution to journalArticle

9 Citations (Scopus)


Crystal structures of transmembrane transport proteins belonging to the important families of neurotransmitter-sodium symporters reveal how they transport neurotransmitters across membranes. Substrate-induced structural conformations of gated neurotransmitter-sodium symporters have been in the focus of research, however, a key question concerning the mechanism of Na+ ion coupling remained unanswered. Homology models of human glial transporter subtypes of the major inhibitory neurotransmitter γ-aminobutyric acid were built. In accordance with selectivity data for subtype 2 vs. 3, docking and molecular dynamics calculations suggest similar orthosteric substrate (inhibitor) conformations and binding crevices but distinguishable allosteric Zn2+ ion binding motifs. Considering the occluded conformational states of glial human γ-aminobutyric acid transporter subtypes, we found major semi-extended and minor ring-like conformations of zwitterionic γ-aminobutyric acid in complex with Na+ ion. The existence of the minor ring-like conformation of γ-aminobutyric acid in complex with Na+ ion may be attributed to the strengthening of the intramolecular H-bond by the electrostatic effect of Na+ ion. Coupling substrate uptake into cells with the thermodynamically favorable Na+ ion movement through substrate-Na+ ion complex formation may be a mechanistic principle featuring transmembrane neurotransmitter-sodium symporter proteins.

Original languageEnglish
Pages (from-to)210-214
Number of pages5
JournalBiochemical and biophysical research communications
Issue number2
Publication statusPublished - Jul 24 2009


  • Charge-assisted hydrogen bonding
  • Glial subtypes of human γ-aminobutyric acid transporters
  • Homology modeling
  • Molecular dynamics
  • Neurotransmitter-sodium symporters
  • Substrate docking
  • Substrate-Na ion complex
  • Zinc ion

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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