2019 AMI Online Salon

GLP-1R and Biased Agonism

Project Details

  • Entrant Name: Logan Weihe

  • Membership Type: Student Submission

  • Other Contributors:                         

  • Address: Chicago,IL

  • Client: University of Illinois at Chicago

  • Medium/software used: Visual Molecular Dynamics, Pixologic ZBrush, Adobe Photoshop, Keyshot

  • Final presentation format: Informational Poster

  • Primary Audience: Medical Professional

Project Description

Mainly intended for a medical professional audience, this poster focuses on the class B G-protein-coupled receptor GLP-1R and the G-protein GLP-1. These molecules are involved in the stimulation of insulin secretion, making GLP-1R a significant target for the potential treatment of diabetes and obesity. This poster highlights the specific residues that are important in the pharmacology of GLP-1R, and are essential in understanding how to create novel therapeutics. Residues D372 and E373 found in extracellular loop 3 may contribute to biased agonism in which individual ligands acting at the same GPCR can elicit distinct profiles of signaling and regulation. It has been shown that mutation of these 2 residues highlighted substantially reduces GLP-1 affinity and signaling but has little effect on Exendin function. The visuals present an overall representation of GLP-1R and bound ligand Exendin, as well as a closer view of extracellular loop 3 and its key residues.