A hydrophobic site on the GLP-1 receptor extracellular domain orients the peptide ligand for signal transduction.

ABSTRACT: Structure-function studies have analyzed substitutions within the glucagon-like peptide-1 (GLP-1) sequence that increase resistance to proteolysis, however, the investigation into how such substitutions alter interactions at the GLP-1 receptor (GLP-1R) has captured less attention. This work describes our efforts at identifying relevant interactions between peptide ligands and the GLP-1R extracellular domain that contribute to the positioning of the peptide N-terminus for receptor activation. Alanine substitutions at hydrophilic (Glu127⁎ and Glu128⁎) and hydrophobic (Leu32⁎) GLP-1R residues were previously shown to differentially interact with GLP-1 and exendin-4. We examined if these receptor residues influence the activity of GLP-1- and exendin-4-based peptides containing either alanine o

SUBMITTER: Patterson JT 

PROVIDER: S-EPMC3817388 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature