Inhibitory mechanism of an allosteric antibody targeting the glucagon receptor
S Mukund, Y Shang, HJ Clarke, A Madjidi… - Journal of Biological …, 2013 - ASBMB
Elevated glucagon levels and increased hepatic glucagon receptor (GCGR) signaling
contribute to hyperglycemia in type 2 diabetes. We have identified a monoclonal antibody
that inhibits GCGR, a class B G-protein coupled receptor (GPCR), through a unique
allosteric mechanism. Receptor inhibition is mediated by the binding of this antibody to two
distinct sites that lie outside of the glucagon binding cleft. One site consists of a patch of
residues that are surface-exposed on the face of the extracellular domain (ECD) opposite …
contribute to hyperglycemia in type 2 diabetes. We have identified a monoclonal antibody
that inhibits GCGR, a class B G-protein coupled receptor (GPCR), through a unique
allosteric mechanism. Receptor inhibition is mediated by the binding of this antibody to two
distinct sites that lie outside of the glucagon binding cleft. One site consists of a patch of
residues that are surface-exposed on the face of the extracellular domain (ECD) opposite …
