2019-05-21 11:00 ~ 2019-05-21 12:00
Venue: IBC R209
Speaker: Dr. Daniel Nietlispach
Current Position: Reader in biomolecular NMR spectroscopy, Department of Biochemistry, University of Cambridge, UK
Host: Dr. Ming-Daw Tsai & Dr. Wen-Jin Wu
Abstract:
G-protein-coupled receptors (GPCRs) are a large family of membrane embedded proteins that activate a multitude of signalling pathways triggering various cellular responses in health and disease. The last decade has led to a surge of receptor structures through crystallography, and more recently cryo-EM. This has helped to develop a static picture of these receptors in mostly inactive but also active states and in complex with cytoplasmic binding partners such as heterotrimeric G-proteins, β-arrestins and their mimetics. However, despite this wealth of static information, key questions related to GPCR function and mechanism of action are persisting due to the intrinsically dynamic nature of these receptors. We use 1H,13C NMR spectroscopy to investigate ligand based activation and basal activity of the β1 adrenergic receptor (β1AR).1,2 In our work we find evidence for the existence of novel active receptor states and a level of receptor plasticity in ternary complexes, which can be related to the pharmacological concept of partial agonism. Our NMR data connects receptor activity to the presence of μs-to-ms timescale dynamics and shows β1AR as a highly adaptable molecular signalling entity.-Dr. Daniel Nietlispach
Contact person: Ms. Nancy Liu
Tel: 02-27855696#2061
Email: liukchun@gate.sinica.edu.tw
Institute of Biological Chemistry, Academia Sinica
