Predicted structure of agonist-bound glucagon-like peptide 1 receptor, a class B G protein-coupled receptor.

ABSTRACT: The glucagon-like peptide 1 receptor (GLP1R) is a G protein-coupled receptor (GPCR) involved in insulin synthesis and regulation; therefore, it is an important drug target for treatment of diabetes. However, GLP1R is a member of the class B1 family of GPCRs for which there are no experimental structures. To provide a structural basis for drug design and to probe class B GPCR activation, we predicted the transmembrane (TM) bundle structure of GLP1R bound to the peptide Exendin-4 (Exe4; a GLP1R agonist on the market for treating diabetes) using the MembStruk method for scanning TM bundle conformations. We used protein-protein docking methods to combine the TM bundle with the X-ray crystal structure of the 143-aa N terminus coupled to the Exe4 peptide. This complex was subjected to 28 ns of f

SUBMITTER: Kirkpatrick A 

PROVIDER: S-EPMC3523846 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature