Full-length GLP-1R

Glucagon Like Peptide-1 Receptor (GLP-1R) belongs to Class B family that include a large extracellular domain (ECD) and the 7transmembrane domain (7 TMD). It is a typically peptide-binding receptor, natural peptide ligand of which is GLP-1, expressed from three major tissues in humans: enteroendocrine L cells in the distal intestine, (; cells in the pancreas, and the central nervous system. The main action of GLP-1 is to work as an incretin to increase the insulin release in the presence of high glucose level. The current view is that GLP-1 are responsible for most incretin activity normally observed, because of that, GLP-1R is always a hot drug target for the T2DM curing. There are several market drugs target on GLP-1R (Figure 1). So, the structural and functional research of GLP-1R have a great effect on drugs optimization and new drugs design. In the past several years, there are four ECD complex with antibody and different peptides structure determined (Figure 2). But there is no any full-length GLP-1R structure solved, which limits our understanding of activation mechanism of GLP-1R. We are aim at to solve the structure of Full-length GLP-1R and reveals the peptide-binding mechanism, which will provide useful information for the further function study and new drugs design. According to protein engineering and compounds screening, we have got the stable construct and screened co-crystal ligands. In the future works, we will focus on the crystallization trials of FL-GLP-1R-peptide complex and FL-GLP-1R-antibody complex and hopes that they can help us look insight into the whole Class B family and peptide-binding GPCRs family.