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

FEBS Lett. 2002 Oct 23;530(1-3):244-8. doi: 10.1016/s0014-5793(02)03492-0.

Abstract

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.

MeSH terms

  • Aspartic Acid / metabolism*
  • Cell Line
  • Glucagon / chemistry
  • Glucagon / metabolism*
  • Glucagon-Like Peptide 1
  • Glucagon-Like Peptide-1 Receptor
  • Humans
  • Mutagenesis, Site-Directed
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism*
  • Protein Precursors / chemistry
  • Protein Precursors / metabolism*
  • Radioligand Assay
  • Receptors, Glucagon / genetics
  • Receptors, Glucagon / metabolism*

Substances

  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Peptide Fragments
  • Protein Precursors
  • Receptors, Glucagon
  • Aspartic Acid
  • Glucagon-Like Peptide 1
  • Glucagon