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The positive charge at Lys‐288 of the glucagon‐like peptide‐1 (GLP‐1) receptor is important for binding the N‐terminus of peptide agonists
Author(s) -
Al-Sabah Suleiman,
Donnelly Dan
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)01043-3
Subject(s) - peptide , receptor , glucagon like peptide 1 receptor , chemistry , residue (chemistry) , peptide hormone , biochemistry , n terminus , glucagon , agonist , glucagon like peptide 1 , c terminus , lysine , peptide sequence , stereochemistry , hormone , amino acid , biology , endocrinology , gene , type 2 diabetes , diabetes mellitus
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.