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PDBsum entry 7jv5
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Signaling protein
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PDB id
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7jv5
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Contents |
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282 a.a.
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238 a.a.
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339 a.a.
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57 a.a.
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128 a.a.
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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 insights into the human d1 and d2 dopamine receptor signaling complexes.
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Authors
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Y.Zhuang,
P.Xu,
C.Mao,
L.Wang,
B.Krumm,
X.E.Zhou,
S.Huang,
H.Liu,
X.Cheng,
X.P.Huang,
D.D.Shen,
T.Xu,
Y.F.Liu,
Y.Wang,
J.Guo,
Y.Jiang,
H.Jiang,
K.Melcher,
B.L.Roth,
Y.Zhang,
C.Zhang,
H.E.Xu.
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Ref.
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Cell, 2021,
184,
931.
[DOI no: ]
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PubMed id
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Abstract
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The D1- and D2-dopamine receptors (D1R and D2R), which signal through
Gs and Gi, respectively, represent the principal
stimulatory and inhibitory dopamine receptors in the central nervous system. D1R
and D2R also represent the main therapeutic targets for Parkinson's disease,
schizophrenia, and many other neuropsychiatric disorders, and insight into their
signaling is essential for understanding both therapeutic and side effects of
dopaminergic drugs. Here, we report four cryoelectron microscopy (cryo-EM)
structures of D1R-Gs and D2R-Gi signaling complexes with
selective and non-selective dopamine agonists, including two currently used
anti-Parkinson's disease drugs, apomorphine and bromocriptine. These structures,
together with mutagenesis studies, reveal the conserved binding mode of dopamine
agonists, the unique pocket topology underlying ligand selectivity, the
conformational changes in receptor activation, and potential structural
determinants for G protein-coupling selectivity. These results provide both a
molecular understanding of dopamine signaling and multiple structural templates
for drug design targeting the dopaminergic system.
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