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The mechanism of agonist activation of the `Family B' G protein-coupled receptor for glucagon-like peptide-1 (GLP-1)

Reference	C14539
Principal Investigator / Supervisor	Dr Daniel Donnelly
Co-Investigators / Co-Supervisors	Professor John B C Findlay
Institution	University of Leeds
Department	Institute of Membrane & Systems Biology
Funding type	Research
Value (£)	167,196
Status	Completed
Type	Research Grant
Start date	01/04/2001
End date	15/11/2004
Duration	43 months

Abstract

Evidence suggests that there are distinct determinants for ligand binding and receptor activation for the glucagon-like peptide-1 receptor (GLP-1R). For example, subtle alterations (e.g. Asp-9 to Glu) to the structure of the high-affinity GLP-1R agonist, exendin(2-39), result in its conversion from a potent agonist to an antagonist without reducing binding affinity. Furthermore, a double mutation in the first extracellular loop of GLP-1R results in a reduction of the ability of GLP-1 to activate the receptor despite no significant loss in affinity or receptor density. These alterations to the structure, of either the ligand or the receptor, interfere with the receptor activation process without affecting ligand affinity. Further analysis of the activation process will provide useful tools for probing the mechanism of agonist-induced receptor activation.

Summary

unavailable

Committee	Closed Committee - Biochemistry & Cell Biology (BCB)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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