Meet Dr. GPCR Summit Partners
- Click to Explore -
GPCR activation mechanisms across classes and macro/micro scales
Wednesday, 09/15/2021 @ 2:00 PM - EST
- Dr. David Gloriam -
- The University of Copenhagen -
- The University of Copenhagen -
- Copenhagen, Denmark -
Abstract
Two-thirds of human hormones and one-third of clinical drugs activate ~350 G protein-coupled receptors belonging to four classes: A, B1, C, and F. Whereas a model of activation has been described for class A, very little is known about the activation of the other classes which differ by being activated by endogenous ligands bound mainly or entirely extracellularly. Here, we show that although they use the same structural scaffold and share several helix macro switches, the GPCR classes differ in their microswitch residue positions and contacts. We present molecular mechanistic maps of activation for each GPCR class and new methods for contact analysis applicable for any functional determinants. This is the first superfamily residue-level rationale for conformational selection and allosteric communication by ligands and G proteins laying the foundation for receptor-function studies and drugs with the desired modality.
About Dr. David Gloriam
David Gloriam is a Professor in Computational Receptor Biology at the University of Copenhagen where he leads a research cluster for GPCR function and drug discovery and a Pharmaceutical Data Science unit. His group runs the GPCRdb database where ~4,000 researchers each month retrieve reference data and access online tools for analysis, visualization, and experiment design.
He got his Ph.D. from Uppsala University, Sweden including the bioinformatic identification of 24 novels human G protein-coupled receptors. He later identified physiological hormones of such under characterized ‘orphan’ receptors and functional probes for a range of receptors. He made two postdocs in the UK at the EMBL-European Bioinformatics Institute and GlaxoSmithKline. In 2018 he joined the University of Copenhagen, where he has received an ERC Starting Grant, Lundbeck Foundation Fellowship, and Novo Nordisk Foundation Ascending Investigator awards.
Gloriam is a corresponding member of the Nomenclature Committee of the International Union of Pharmacology (IUPHAR). He is one of the coordinators of recommendations to describe ligand bias towards signaling probes and safer drugs and his group recently developed an online resource of biased ligands and pathway effects to advance the biased signaling field.
Dr. David Gloriam on the web
Meet Dr. GPCR Summit Partners
- Click to Explore -
