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PDBsum entry 5c1m
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Signaling protein/antagonist
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PDB id
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5c1m
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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 µ-Opioid receptor activation.
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Authors
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W.Huang,
A.Manglik,
A.J.Venkatakrishnan,
T.Laeremans,
E.N.Feinberg,
A.L.Sanborn,
H.E.Kato,
K.E.Livingston,
T.S.Thorsen,
R.C.Kling,
S.Granier,
P.Gmeiner,
S.M.Husbands,
J.R.Traynor,
W.I.Weis,
J.Steyaert,
R.O.Dror,
B.K.Kobilka.
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Ref.
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Nature, 2015,
524,
315-321.
[DOI no: ]
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PubMed id
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Abstract
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Activation of the μ-opioid receptor (μOR) is responsible for the efficacy of
the most effective analgesics. To shed light on the structural basis for μOR
activation, here we report a 2.1 Å X-ray crystal structure of the murine μOR
bound to the morphinan agonist BU72 and a G protein mimetic camelid antibody
fragment. The BU72-stabilized changes in the μOR binding pocket are subtle and
differ from those observed for agonist-bound structures of the β2-adrenergic
receptor (β2AR) and the M2 muscarinic receptor. Comparison with active β2AR
reveals a common rearrangement in the packing of three conserved amino acids in
the core of the μOR, and molecular dynamics simulations illustrate how the
ligand-binding pocket is conformationally linked to this conserved triad.
Additionally, an extensive polar network between the ligand-binding pocket and
the cytoplasmic domains appears to play a similar role in signal propagation for
all three G-protein-coupled receptors.
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