The glucagon‐like peptide‐1 receptor binding site for the N‐terminus of GLP‐1 requires polarity at Asp198 rather than negative charge

FEBS Letters

Donnelly, Dan¹  López de Maturana, Rakel¹ 

[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(7–36)amide;    Antagonist;    Exendin;    GLP-1;    glucagon-like peptide-1(7–36)amide;    DMEM;    Dulbecco's modified Eagle's medium;    GPCR;    G protein-coupled receptor;   

DOI  :  10.1016/S0014-5793(02)03492-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The mutation of Asp198 to Asn in the receptor for glucagon-like peptide-1(7–36)amide (GLP-1) had no effect upon GLP-1 affinity whereas substitution with Ala greatly reduced affinity, demonstrating the importance of polarity rather than negative charge at Asp198. However, the Asp198-Ala mutation had less effect upon the affinity of Exendin-4, a peptide agonist that has been shown previously not to require its N-terminus for high affinity. Moreover, the affinity of a truncated GLP-1 analogue lacking the first eight residues was not affected by the Asp198-Ala mutation, demonstrating that Asp198 is required for maintaining the binding site of the N-terminal region of GLP-1.

【 授权许可】

Unknown