Different Protein Receptor Responses Resulting from Different Membrane Environments

Published May 24, 2023

Receptor proteins respond differently to drugs depending on the environment in which they are studied.

Special protein-coupled receptors play a role in nearly all physiological responses and are targets for more than 1/3 of all FDA-approved drugs. State-of-the art instrumentation at the MagLab allowed researchers to explore the effects of different lipid compositions on receptor activation, hinting that hereditary or dietary factors may influence the effectiveness of drugs.

What did scientists discover?

This interdisciplinary research team showed how phospholipids in the cellular environment can influence the drug response of receptor proteins and thereby alter cellular signaling by those receptor proteins.

Why is this important?

One (or more) of the eight-hundred human G protein-coupled receptors (GPCRs) play a role in nearly all physiological responses. As such, GPCRs are targets for more than one-third of all FDA-approved drugs. The findings from this study imply that hereditary factors or dietary factors that alter lipid compositions of cells may influence the effectiveness of drugs.

Who did the research?

N. Thakur¹, A.P. Ray¹, L. Sharp², B. Jin¹, A. Duong¹, N. Gopal Pour¹, S. Obeng³, A.V. Wijesekara¹, Z.-G. Gao⁴, C.R. McCurdy³, K.A. Jacobson⁴, E. Lyman², M.T. Eddy¹

¹University of Florida, Dept. of Chemistry ²University of Delaware, Dept. of Physics and Astronomy ³University of Florida, Dept. of Medicinal Chemistry ⁴Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health

Why did they need the MagLab?

NMR spectroscopy can observe different three-dimensional conformations of protein receptors and determine how drugs and lipids impact these conformations that correlate with changes in receptor function. State-of-the-art NMR instrumentation at the MagLab’s AMRIS Facility is uniquely suited for precise measurements of lipid compositions and simultaneous investigation of receptor protein conformations because it enables the visualization of multiple different nuclei of importance to these studies, in particular 1H, 19F, and 31P

Details for scientists

View or download the expert-level Science Highlight, Different Protein Receptor Responses Resulting from Different Membrane Environments
Read the full-length publication, Anionic Phospholipids Control Mechanisms of GPCR-G Protein Recognition, in Nature Communications Data Set 1, Data Set 2

Funding

This research was funded by the following grants: Boebinger (NSF DMR-2128556); Eddy (NIH R35GM138291), Lyman (R01GM120351), Gao and Jin (ZIA DK031117)

For more information, contact Joanna Long.