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PDBsum entry 4ms3
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Signaling protein/agonist
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PDB id
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4ms3
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References listed in PDB file
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Key reference
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Title
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Structural mechanism of ligand activation in human gaba(b) receptor.
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Authors
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Y.Geng,
M.Bush,
L.Mosyak,
F.Wang,
Q.R.Fan.
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Ref.
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Nature, 2013,
504,
254-259.
[DOI no: ]
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PubMed id
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Abstract
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Human GABA(B) (γ-aminobutyric acid class B) receptor is a G-protein-coupled
receptor central to inhibitory neurotransmission in the brain. It functions as
an obligatory heterodimer of the subunits GBR1 and GBR2. Here we present the
crystal structures of a heterodimeric complex between the extracellular domains
of GBR1 and GBR2 in the apo, agonist-bound and antagonist-bound forms. The apo
and antagonist-bound structures represent the resting state of the receptor; the
agonist-bound complex corresponds to the active state. Both subunits adopt an
open conformation at rest, and only GBR1 closes on agonist-induced receptor
activation. The agonists and antagonists are anchored in the interdomain crevice
of GBR1 by an overlapping set of residues. An antagonist confines GBR1 to the
open conformation of the inactive state, whereas an agonist induces its domain
closure for activation. Our data reveal a unique activation mechanism for
GABA(B) receptor that involves the formation of a novel heterodimer interface
between subunits.
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