Structural basis for constitutive activity and agonist-induced activation of the enteroendocrine fat sensor GPR119.

ABSTRACT:

Background and purpose

GPR119 is a Gαs-coupled 7TM receptor activated by endogenous lipids such as oleoylethanolamide (OEA) and by the dietary triglyceride metabolite 2-monoacylglycerol. GPR119 stimulates enteroendocrine hormone and insulin secretion. But despite massive drug discovery efforts in the field, very little is known about the basic molecular pharmacology of GPR119.

Experimental approach

GPR119 receptor signalling was studied in transfected cells. Mutational mapping (30 mutations in 23 positions) was performed on residues required for ligand-independent and agonist-induced GPR119 activation (AR231453 and OEA). Novel Rosetta-based receptor modelling was applied, using a composite template approach with segments from different X-ray structures and fully flexible lig

SUBMITTER: Engelstoft MS 

PROVIDER: S-EPMC4290716 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature