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PDBsum entry 6os0
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Membrane protein
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PDB id
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6os0
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References listed in PDB file
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Key reference
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Title
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Angiotensin and biased analogs induce structurally distinct active conformations within a gpcr.
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Authors
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L.M.Wingler,
M.A.Skiba,
C.Mcmahon,
D.P.Staus,
A.L.W.Kleinhenz,
C.M.Suomivuori,
N.R.Latorraca,
R.O.Dror,
R.J.Lefkowitz,
A.C.Kruse.
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Ref.
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Science, 2020,
367,
888-892.
[DOI no: ]
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PubMed id
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Abstract
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Biased agonists of G protein-coupled receptors (GPCRs) preferentially activate a
subset of downstream signaling pathways. In this work, we present crystal
structures of angiotensin II type 1 receptor (AT1R) (2.7 to 2.9 angstroms) bound
to three ligands with divergent bias profiles: the balanced endogenous agonist
angiotensin II (AngII) and two strongly β-arrestin-biased analogs. Compared
with other ligands, AngII promotes more-substantial rearrangements not only at
the bottom of the ligand-binding pocket but also in a key polar network in the
receptor core, which forms a sodium-binding site in most GPCRs. Divergences from
the family consensus in this region, which appears to act as a biased signaling
switch, may predispose the AT1R and certain other GPCRs (such as chemokine
receptors) to adopt conformations that are capable of activating β-arrestin but
not heterotrimeric Gq protein signaling.
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