Description
Title: GPCR Conformational Heterogeneity DEER Analysis
Abstract: G protein-coupled receptors (GPCRs) are a diverse class of transmembrane helical proteins that are essential pharmacological targets because they are involved in a variety of physiological signaling pathways. Few factors, such as receptor basal activity, ligand affinity, intrinsic efficacy, and signal bias, determine GPCR function and the effects of therapeutic molecules. These parameters are encoded in the distinctive receptor conformations that are present in equilibrium and their populations, which are therefore of utmost importance for comprehending receptor (mal-)functions and logically designing enhanced therapeutics. In order to accomplish this, the combination of site-directed spin labeling and EPR spectroscopy, in particular double electron-electron resonance (DEER), is incredibly useful because it has access to sub-Angstrom spatial resolution and gives a thorough account of the number and populations of equilibrium conformations. An overview of current DEER studies on GPCRs is provided in this review, with an emphasis on the definition of structure/function frameworks and a discussion of recent advancements in data analysis and visualization. We define “conformational efficacy” as a parameter, accounting for the loose coupling between receptor segments seen for various GPCRs using DEER, to describe ligand-specific shifts in the conformational equilibrium.
Keywords: G protein-coupled receptor; GPCR; 7TM receptor; G protein; arrestin; structure; function;
structural plasticity; electron paramagnetic resonance; EPR; DEER; pELDOR
Paper Quality: SCOPUS / Web of Science Level Research Paper
Subject: Biomolecules
Writer Experience: 20+ Years
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