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PDBsum entry 5xf1
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Signaling protein
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PDB id
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5xf1
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Contents |
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544 a.a.
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496 a.a.
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231 a.a.
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214 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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Structure of the full-Length glucagon class b g-Protein-Coupled receptor.
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Authors
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H.Zhang,
A.Qiao,
D.Yang,
L.Yang,
A.Dai,
C.De graaf,
S.Reedtz-Runge,
V.Dharmarajan,
H.Zhang,
G.W.Han,
T.D.Grant,
R.G.Sierra,
U.Weierstall,
G.Nelson,
W.Liu,
Y.Wu,
L.Ma,
X.Cai,
G.Lin,
X.Wu,
Z.Geng,
Y.Dong,
G.Song,
P.R.Griffin,
J.Lau,
V.Cherezov,
H.Yang,
M.A.Hanson,
R.C.Stevens,
Q.Zhao,
H.Jiang,
M.W.Wang,
B.Wu.
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Ref.
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Nature, 2017,
546,
259-264.
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PubMed id
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Abstract
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The human glucagon receptor, GCGR, belongs to the class B G-protein-coupled
receptor family and plays a key role in glucose homeostasis and the
pathophysiology of type 2 diabetes. Here we report the 3.0 Å crystal
structure of full-length GCGR containing both the extracellular domain and
transmembrane domain in an inactive conformation. The two domains are connected
by a 12-residue segment termed the stalk, which adopts a β-strand conformation,
instead of forming an α-helix as observed in the previously solved structure of
the GCGR transmembrane domain. The first extracellular loop exhibits a
β-hairpin conformation and interacts with the stalk to form a compact β-sheet
structure. Hydrogen-deuterium exchange, disulfide crosslinking and molecular
dynamics studies suggest that the stalk and the first extracellular loop have
critical roles in modulating peptide ligand binding and receptor activation.
These insights into the full-length GCGR structure deepen our understanding of
the signalling mechanisms of class B G-protein-coupled receptors.
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