Recombinant Human Glucagon receptor (GCGR)-VLPs

1. 3.0 A-resolution crystal structure of the full-length human glucagon receptor (GCGR) in complex with a glucagon analogue and partial agonist, NNC1702 PMID:29300013
2. work toward the mapping of interactions between the polypeptide hormone glucagon and the glucagon receptor PMID:28508109
3. 3.0 A crystal structure of full-length GCGR containing both the extracellular domain and transmembrane domain in an inactive conformation PMID:28514451
4. This work suggests that RAMP2 may modify the agonist activity and trafficking of the GCGR, with potential relevance to production of new peptide analogs with selective agonist activities. PMID:28586439
5. Data suggest that GCGR activation proceeds via a mechanism in which transmembrane helix 6 (TM6) is held in an inactive conformation by a conserved polar core and a hydrophobic lock (involving intracellular loop 3, IC3); mutations in the corresponding polar core of GCGR disrupt these inhibitory elements, allow TM6 to swing outward, and induce constitutive G protein signaling. PMID:28356352
6. The activation of the GCGR is characterized by the outward movement of the intracellular side of helix VI. In the active state of the GCGR, the Arg173(2.46)-Ser350(6.41) and Glu245(3.50)-Thr351(6.42) hydrogen bonds break, and the chi1 rotamer of Phe322(5.54) changes from perpendicular to parallel to helix VI. PMID:27094704
7. In the glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R), the extracellular domain is required for signaling even when the hormone is covalently linked to the transmembrane domain. PMID:27226600
8. 2.5 A crystal structure of human GCGR in complex with the antagonist MK-0893, which is found to bind to an allosteric site outside the seven transmembrane helical bundle in a position between TM6 and TM7 extending into the lipid bilayer PMID:27111510
9. Molecular dynamics and disulfide crosslinking studies suggest that apo-GCGR can adopt both an open and closed conformation associated with extensive contacts between the ECD and 7TM domain. Glucagon binds to GCGR by a conformational selection mechanism. PMID:26227798
10. glucagon cell adenomatosis with GCGR germline mutations seems to follow an autosomal-recessive trait. PMID:25695890
11. Using a real-time time-resolved FRET-based internalization assay, we show that GLP-1R, GIPR, and GCGR internalize with differential properties PMID:25451942
12. crystal structure of the seven transmembrane helical domain of human GCGR at 3.4 A resolution, and a hybrid model of glucagon bound to GCGR to understand the molecular recognition of the receptor for its native ligand PMID:23863937
13. Letter/Case Report: nonfunctional glucagon cell adenomatosis with no detectable glucagon receptor mutations. PMID:23407487
14. GRA1 is a potent glucagon receptor antagonist with strong antihyperglycemic efficacy in preclinical models and prominent effects on hepatic gene-expression related to amino acid metabolism PMID:23185367
15. F22, V23, M27, and D15 of GCGR are the most important residues for glucagon binding. PMID:22893257
16. in addition to activation of the classic cAMP/protein kinase A (PKA) pathway, activation of GCGR also induced beta-catenin stabilization and activated beta-catenin-mediated transcription PMID:22438981
17. analysis of glucagon receptor antagonists with reduced molecular weight and lipophilicity PMID:22119466
18. The P86S mutant GCGR shows abnormal receptor internalization & calcium mobilization, & causes apoptosis. It cases Mahvash disease (hyperglucagonemia, hypoglycemia, pancreatic neuroendocrine tumors). PMID:21680267
19. substituted cysteine accessibility method and 3D-molecular modeling to study the N-terminal domain; results showed that Asp(63), Arg(116), and Lys(98) are essential for the receptor structure and/or ligand binding PMID:20647307
20. The [Ca2+] response is induced by glucagon mainly via the coupling of GCGR to the Galphaq/11 and Galphai/o proteins. PMID:19903011
21. The Gly40Ser polymorphism of the GCGR gene is associated with higher risk of hypertension and with enhanced proximal tubular sodium reabsorption. PMID:11692154
22. Gly40Ser mutation in the glucagon receptor gene is not associated with type 2 diabetes in a Brazilian population, but a reduction of insulin secretion was observed in Gly40Ser carriers. PMID:11961492
23. Three distinct epitopes on the extracellular face of the glucagon receptor determine specificity for the glucagon amino terminus PMID:12724331
24. Expression of peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha), known to be upregulated in the liver by fasting, was found to abolish the cAMP-dependent downregulation of glucagon receptor mRNA expression in vitro. PMID:17374560

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HGNC: 4192

UNIGENE: Hs.208

KEGG: hsa:2642

STRING: 9606.ENSP00000383558

OMIM: 138033