Site-specific fluorescence reveals distinct structural changes with GABA receptor activation and antagonism

Yongchang Chang, David S. Weiss

Research output: Contribution to journalArticle

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Neurotransmitter-operated ion channels, such as the GABA (γ-aminobutyric acid) receptor, are important in fast synaptic transmission between neurons. Using site-specific fluorescent labeling and simultaneous electrophysiological analysis in Xenopus laevis oocytes expressing recombinant ρ1 GABA receptors, we identified agonist-mediated molecular rearrangements at three positions within and near the agonist-binding pocket that were highly correlated with receptor activation. We also show that competitive antagonists induced distinct rearrangements on their own that stabilized the receptor in a closed state. Finally, the allosteric antagonist picrotoxin induced a global conformational change that was sensed in the subunit-subunit interface of the amino (N)-terminal domain, distant from its presumed site of action within the transmembrane domains. This first detection in real time of molecular rearrangements of a ligand-activated receptor provides insights into the structural correlates of activation, antagonism and allosteric modulation.

Original languageEnglish (US)
Pages (from-to)1163-1168
Number of pages6
JournalNature Neuroscience
Issue number11
Publication statusPublished - Nov 2002


ASJC Scopus subject areas

  • Neuroscience(all)

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