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Substrate-Na+ complex formation: coupling mechanism for gamma-aminobutyrate symporters
- Source :
- Biochemical and biophysical research communications. 385(2)
- Publication Year :
- 2009
-
Abstract
- 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 gamma-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 Zn(2+) ion binding motifs. Considering the occluded conformational states of glial human gamma-aminobutyric acid transporter subtypes, we found major semi-extended and minor ring-like conformations of zwitterionic gamma-aminobutyric acid in complex with Na(+) ion. The existence of the minor ring-like conformation of gamma-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.
- Subjects :
- Models, Molecular
GABA Plasma Membrane Transport Proteins
Protein Conformation
Allosteric regulation
Amino Acid Motifs
Biophysics
Biochemistry
Ion
Ion binding
Allosteric Regulation
Humans
Homology modeling
Molecular Biology
gamma-Aminobutyric Acid
Crystallography
Chemistry
Sodium
Cell Biology
Membrane transport
Transmembrane protein
Zinc
Docking (molecular)
Symporter
Protein Binding
Subjects
Details
- ISSN :
- 10902104
- Volume :
- 385
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Biochemical and biophysical research communications
- Accession number :
- edsair.doi.dedup.....2c32b300e889e1bc30a3b267166ebc2a