Abstract
Lysine-288 in the glucagon-like peptide-1 receptor was predicted to be ideally positioned to play a role in hormone binding. Subsequent mutation of Lys-288 to Ala or Leu greatly reduced hormone affinity, while substitution with Arg had minimal effect. Compared to wild type, the Lys288-Ala receptor had a reduced affinity for three peptide ligands with complete N-terminal sequences but not for their N-truncated analogues. Hence, the role of this positively charged residue, which is conserved at the equivalent position in all other Family B receptors, was determined to be important for receptor interaction with the N-terminal eight residues of peptide agonists.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Amino Acid Substitution
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Binding, Competitive
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Cells, Cultured
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Cyclic AMP / analysis
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Cyclic AMP / metabolism
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Exenatide
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Glucagon-Like Peptide-1 Receptor
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Humans
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Inhibitory Concentration 50
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Kidney / cytology
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Ligands
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Lysine / chemistry*
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Lysine / genetics
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Lysine / metabolism*
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Molecular Sequence Data
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Peptide Fragments / pharmacology
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Peptides / pharmacology
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Radioligand Assay
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Receptors, Glucagon / antagonists & inhibitors
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Receptors, Glucagon / chemistry*
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Receptors, Glucagon / genetics
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Receptors, Glucagon / metabolism*
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Recombinant Proteins / antagonists & inhibitors
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Sequence Homology, Amino Acid
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Transfection
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Venoms*
Substances
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GLP1R protein, human
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Glucagon-Like Peptide-1 Receptor
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Ligands
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Peptide Fragments
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Peptides
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Receptors, Glucagon
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Recombinant Proteins
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Venoms
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exendin (9-39)
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Exenatide
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Cyclic AMP
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Lysine