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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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PDB id:
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| Name: |
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Membrane protein
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Title:
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Crystal structure of thermostabilised full-length glp-1r in complex with a truncated peptide agonist at 3.7 a resolution
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Structure:
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Glucagon-like peptide 1 receptor. Chain: a. Fragment: unp residues 24-432. Synonym: glp-1r. Engineered: yes. Mutation: yes. Truncated peptide agonist. Chain: b. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: glp1r. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Synthetic: yes. Synthetic construct. Organism_taxid: 32630
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Resolution:
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3.70Å
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R-factor:
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0.287
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R-free:
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0.334
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Authors:
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M.Rappas,A.Jazayeri,A.J.H.Brown,J.Kean,J.C.Errey,N.Robertson,C.Fiez- Vandal,S.P.Andrews,M.Congreve,A.Bortolato,J.S.Mason,A.H.Baig, I.Teobald,A.S.Dore,M.Weir,R.M.Cooke,F.H.Marshall
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Key ref:
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A.Jazayeri
et al.
(2017).
Crystal structure of the GLP-1 receptor bound to a peptide agonist.
Nature,
546,
254-258.
PubMed id:
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Date:
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09-May-17
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Release date:
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14-Jun-17
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PROCHECK
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Headers
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References
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P43220
(GLP1R_HUMAN) -
Glucagon-like peptide 1 receptor from Homo sapiens
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Seq:
Struc:
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463 a.a.
389 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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*
PDB and UniProt seqs differ
at 12 residue positions (black
crosses)
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Nature
546:254-258
(2017)
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PubMed id:
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Crystal structure of the GLP-1 receptor bound to a peptide agonist.
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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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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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