Cited by 46Neuroscience and Neuropharmacology ResearchReceptor Mechanisms and SignalingNicotinic Acetylcholine Receptors Study

Local and Global Ligand-Induced Changes in the Structure of the GABAAReceptor

Muroi, Yukiko, Czajkowski, Cynthia, Jackson, Meyer B.·2006·Biochemistry

Abstract

Ligand-gated channels mediate synaptic transmission through conformational transitions triggered by the binding of neurotransmitters. These transitions are well-defined in terms of ion conductance, but their structural basis is poorly understood. To probe these changes in structure, GABA(A) receptors were expressed in Xenopus oocytes and labeled at selected sites with environment-sensitive fluorophores. With labels at two different residues in the alpha1 subunit in loop E of the GABA-binding pocket, GABA elicited fluorescence changes opposite in sign. This pattern of fluorescence changes is consistent with a closure of the GABA-binding cavity at the subunit interface. The competitive antagonist SR-95531 inverted this pattern of fluorescence change, but the noncompetitive antagonist picrotoxin failed to elicit optical signals. In response to GABA (but not SR-95531), labels at the homologous residues in the beta2 subunit showed the same pattern of fluorescence change as the alpha1-subunit labels, indicating a global transition with comparable movements in homologous regions of different subunits. Incorporation of the gamma2 subunit altered the fluorescence changes of alpha1-subunit labels and eliminated them in beta2-subunit labels. Thus, the ligand-induced structural changes in the GABA(A) receptor can extend over considerable distances or remain highly localized, depending upon subunit composition and ligand.

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Crossref · 10.1021/bi060222v

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Authors
Muroi, Y., Czajkowski, C., & Jackson, M. B.
Affiliations
University of Wisconsin–Madison (US)
Corresponding author
Jackson, Meyer B.
Venue
Biochemistry
Published
2006-05-19
Volume
45
Issue
23
Pages
7013-7022
ISSN
  • 0006-2960 (ISSN-L)
  • 1520-4995
OpenAlex
W2114908297
Cited by
46
References
49
Citations by year
2025: 1 · 2024: 1 · 2022: 1 · 2020: 4 · 2019: 1 · 2016: 3 · 2015: 3 · 2014: 3 · 2013: 1 · 2012: 1
FWCI
2.26
Type
journal article
Language
en
Open access
closed
Locations
  • Biochemistry (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Korea Electric Power Corporation
  • National Institute of Neurological Disorders and Stroke (NS34727)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
Keywords
GABAA receptor, ligand-gated ion channels, GABA binding, conformational change, fluorescence resonance energy transfer, alpha1 subunit, beta2 subunit, gamma2 subunit, SR95531, picrotoxin, subunit interface, synaptic transmission
MeSH terms
Animals, Fluorescent Dyes, Ligands, Models, Molecular, Protein Conformation, Receptors, GABA-A, Recombinant Proteins, Spectrometry, Fluorescence, Xenopus laevis, Mutagenesis, Site-Directed, Rats

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