FEB 21, 2018 9:00 AM PST

New Tools for Understanding Allosteric Signaling in G Protein Coupled Receptors

Presented at: Drug Discovery 2018
Speaker
  • Postdoctoral Research Fellow, The Scripps Research Institute
    Biography
      Matthew Eddy received his PhD in physical chemistry from the Massachusetts Institute of Technology in the laboratory of Professor Robert Griffin. During his PhD, Dr. Eddy developed new approaches for using nuclear magnetic resonance (NMR) in the solid state to determine structures of membrane proteins in cellular-like environments. Following his PhD, Dr. Eddy joined the laboratories of Professors Raymond Stevens and Kurt W├╝thrich at The Scripps Research Institute as an American Cancer Society Postdoctoral Fellow. As a postdoctoral fellow, Dr. Eddy used an integrative structural biology approach to study the structures, conformational dynamics, and functions of human G protein-coupled receptors (GPCRs), focusing on the application of nuclear magnetic resonance to improve our understanding of GPCR allosteric function.

    Abstract

    One-third of FDA-approved drugs target G protein-coupled receptors (GPCRs), transmembrane cell surface proteins that recognize small molecules and polypeptides with diverse chemical scaffolds.  When a drug binds to the GPCR extracellular cavity, the information is communicated over 30 Ŭ¬¬ through the plasma membrane to the receptor intracellular surface, inducing changes in the receptor structure that enable complex formation with intracellular partner proteins.  Over the past decade, x-ray crystallography has revealed the three-dimensional structures and binding modes of a growing number of unique GPCR-ligand complexes.  To better understand mechanisms of GPCR activation, this information must be complemented by knowledge of dynamic signaling pathways connecting drug-binding sites to the intracellular surface.  Here we present the development of novel approaches that reveal GPCR signaling pathways with nuclear magnetic resonance (NMR) spectroscopy in solution.  Specific applications of this approach are described for the human A2A adenosine receptor (A2AAR), where NMR uncovers the role of a key allosteric center in drug-induced signal transduction.  Finally, I will discuss the potential extension of these findings and of the presented methods toward studies of other human GPCRs.


    Show Resources
    You May Also Like
    JAN 23, 2020 9:00 AM PST
    C.E. CREDITS
    JAN 23, 2020 9:00 AM PST
    DATE: January 23, 2020 TIME: 9:00am PST, 12:00pm EST...
    APR 07, 2020 8:00 AM PDT
    C.E. CREDITS
    APR 07, 2020 8:00 AM PDT
    DATE: April 7, 2020 TIME: 8:00am PT, 11:00am ET This webinar sets out to establish why quality control is key to robust, reliable, reproducible science. We will look at best practice criteri...
    MAY 08, 2020 10:00 AM PDT
    C.E. CREDITS
    MAY 08, 2020 10:00 AM PDT
    DATE: May 8, 2020 TIME: 10:00am PT, 11:00am MT, 1:00pm ET The application of next generation sequencing to interrogate immune repertoires and methods in which these highly complex dataset...
    MAR 24, 2020 10:00 AM PDT
    C.E. CREDITS
    MAR 24, 2020 10:00 AM PDT
    DATE: March 24, 2020 TIME: 10:00 am PDT, 1:00pm EDT The Clampfit software module is a useful tool to manipulate and analyze electrophysiological data acquired by pCLAMP™ software. Rece...
    APR 16, 2020 9:00 AM PDT
    C.E. CREDITS
    APR 16, 2020 9:00 AM PDT
    DATE: April 16, 2020 TIME: 9:00am PT, 12:00pm ET There is an increasing need to evaluate and understand unique phenotypes and mechanisms of action within the tumor microenvironment. Existing...
    MAR 31, 2020 7:00 AM PDT
    C.E. CREDITS
    MAR 31, 2020 7:00 AM PDT
    DATE: March 31, 2020 TIME: 7:00am PT, 10:00am PT Please join us for this webinar, during which we will present and discuss the promotion of NK cell-driven tumor immunity. In addition, we wil...
    Loading Comments...
    Show Resources