Using integrative biophysical approaches to understand GPCR regulation by β-arrestins
2 March 2023
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Join this webinar to learn how an integrated structural biology workflow can be used to get crucial structural insights on key protein targets that are of therapeutic interest.
About this webinar
G protein-coupled receptors (GPCRs) are a family of seven transmembrane proteins that function to transduce extracellular signals, such as hormones and neurotransmitters, into intracellular signals. To achieve temporal regulation of signalling, a family of proteins known as β-arrestins are responsible for terminating G protein-mediated signalling and desensitising receptors. These β-arrestin proteins are also responsible for mediating the internalisation of most GPCRs, and thus dictating their recycling and re-sensitisation behaviour.
Over the past five years, the work of Dr. John Janetzko and colleagues in Dr. Brian Kobilka’s lab have provided considerable advances in understanding how β-arrestins recognise GPCRs and how these complexes are regulated inside cells. Using cryo-EM, they obtained one of the first structures of a GPCR-β-arrestin complex. This structure showed a bound membrane phosphoinositide, suggesting a possible mode of regulation for these complexes. Using cell-based and in vitro biochemical and biophysical approaches, including hydrogen-deuterium exchange (HDX) MS, they showed that membrane phosphoinositides act as allosteric modulators of GPCR-β-arrestin complexes, gating their assembly and disassembly. Together these studies provide high-resolution molecular details into the mechanism by which these proteins of critical importance for cellular physiology function.
- Learn why Cryo-EM is ideally suited to membrane protein structure determination
- Discover how of HDX mass spectrometry via an integrated structural biology approach can provide critical structural insights for an important class of therapeutics targets.
Dr. John Janetzko, Department of Molecular and Cellular Physiology, Stanford University School of Medicine
Dr. Janetzko obtained his bachelor’s degree in Chemistry from the University of Toronto before attending Harvard University for graduate studies in Chemistry. His graduate work focused on the essential vertebrate enzyme O-GlcNAc transferase in the labs of Drs. Suzanne Walker and Daniel Kahne. After his PhD, he joined Dr. Brian Kobilka’s lab at Stanford University to gain expertise in biophysical approaches to study GPCRs and their transducers. There, his work has focused on understanding the structure and dynamics of GPCR--arrestin complexes.
Dr. Melanie Adams-Cioaba, Senior Director and General Manager of Pharma/Biotech for the electron microscopy business, Thermo Fisher Scientific
Dr. Adams-Cioaba is the Senior Director and General Manager of Pharma/Biotech for the electron microscopy business at Thermo Fisher Scientific. An experienced biochemist and structural biologist, Melanie has a passion for the development and commercialisation of novel solutions for life sciences research. She has previously held business development and management roles at NanoImaging Services, SPT Labtech, and Microlytic North America.