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

FEBS Letters

Al-Sabah, Suleiman¹  Donnelly, Dan¹ 

[1] School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, UK

关键词: G protein-coupled receptor;    Receptor;    Agonist;    Glucagon-like peptide-1;    Antagonist;    Exendin;    GLP-1;    glucagon-like peptide-1(7-36)amide;    GLP-1R;    glucagon-like peptide-1 receptor;    TM;    transmembrane;    ECL;    extracellular loop;   

DOI  :  10.1016/S0014-5793(03)01043-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown