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PDBsum entry 4tk2
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Biosynthetic protein,structural protein
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PDB id
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4tk2
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References listed in PDB file
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Key reference
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Title
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Molecular basis of the alternative recruitment of gaba(a) versus glycine receptors through gephyrin.
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Authors
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H.M.Maric,
V.B.Kasaragod,
T.J.Hausrat,
M.Kneussel,
V.Tretter,
K.Strømgaard,
H.Schindelin.
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Ref.
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Nat Commun, 2014,
5,
5767.
[DOI no: ]
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PubMed id
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Abstract
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γ-Aminobutyric acid type A and glycine receptors (GABAARs, GlyRs) are the major
inhibitory neurotransmitter receptors and contribute to many synaptic functions,
dysfunctions and human diseases. GABAARs are important drug targets regulated by
direct interactions with the scaffolding protein gephyrin. Here we deduce the
molecular basis of this interaction by chemical, biophysical and structural
studies of the gephyrin-GABAAR α3 complex, revealing that the N-terminal region
of the α3 peptide occupies the same binding site as the GlyR β subunit,
whereas the C-terminal moiety, which is conserved among all synaptic GABAAR α
subunits, engages in unique interactions. Thermodynamic dissections of the
gephyrin-receptor interactions identify two residues as primary determinants for
gephyrin's subunit preference. This first structural evidence for the
gephyrin-mediated synaptic accumulation of GABAARs offers a framework for future
investigations into the regulation of inhibitory synaptic strength and for the
development of mechanistically and therapeutically relevant compounds targeting
the gephyrin-GABAAR interaction.
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