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PDBsum entry 5nx2
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Membrane protein
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PDB id
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5nx2
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References listed in PDB file
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Key reference
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Title
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Crystal structure of the glp-1 receptor bound to a peptide agonist.
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Authors
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A.Jazayeri,
M.Rappas,
A.J.H.Brown,
J.Kean,
J.C.Errey,
N.J.Robertson,
C.Fiez-Vandal,
S.P.Andrews,
M.Congreve,
A.Bortolato,
J.S.Mason,
A.H.Baig,
I.Teobald,
A.S.Doré,
M.Weir,
R.M.Cooke,
F.H.Marshall.
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Ref.
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Nature, 2017,
546,
254-258.
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PubMed id
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Abstract
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Glucagon-like peptide 1 (GLP-1) regulates glucose homeostasis through the
control of insulin release from the pancreas. GLP-1 peptide agonists are
efficacious drugs for the treatment of diabetes. To gain insight into the
molecular mechanism of action of GLP-1 peptides, here we report the crystal
structure of the full-length GLP-1 receptor bound to a truncated peptide
agonist. The peptide agonist retains an α-helical conformation as it sits deep
within the receptor-binding pocket. The arrangement of the transmembrane helices
reveals hallmarks of an active conformation similar to that observed in class A
receptors. Guided by this structural information, we design peptide agonists
with potent in vivo activity in a mouse model of diabetes.
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