Dépôt numérique

NMR-based approaches to the study of GPCRs and GPCR-ligand interactions

Pandey, Aditya, Larda, Sacha, Laplante, Steven ORCID: https://orcid.org/0000-0003-2835-5789 et Prosser, Robert Scott (2020). NMR-based approaches to the study of GPCRs and GPCR-ligand interactions In: GPCRs: Structure, Function, and Drug Discovery. Elsevier, Cambridge, MA, p. 65-80.

Ce document n'est pas hébergé sur EspaceINRS.


The structural and atomistic details of G protein-coupled receptors (GPCRs) have been greatly advanced by X-ray crystallography and cryo-electron microscopy. nuclear magnetic resonance (NMR) spectroscopy has the advantage that GPCRs can be further studied from the perspective of a conformational ensemble. Via NMR, one can envisage the activation process in terms of a basis of functional states, whose dynamic interplay can be measured over timescales ranging from picoseconds to seconds. Structural properties of specific states of GPCRs are also available through uniformly 15N and 13C-labeled receptors, although a variety of challenges have slowed progress of structure determination of GPCRs by NMR. In particular, GPCRs are generally difficult to express, purify, and reconstitute under conditions where deuteration and uniform 15N and 13C labeling is achieved. The dynamic nature of most GPCRs, the spectral overlap expected from a heptahelical receptor, and the lack of sample stability over periods of weeks compounds the challenges for NMR structural studies. In this chapter, we review progress with regard to GPCR expression, labeling, and reconstitution in Escherichia coli, insect cells, and yeast. This is discussed in the context of traditional 3D-structure–based approaches and a host of 2D-NMR approaches designed to characterize the conformational ensemble via a combination of uniformly labeled amino acids and 1D-19F NMR studies. Finally, we discuss prospects for drug discovery of GPCRs by focusing on NMR studies of potential ligands.

Type de document: Chapitre de livre
Mots-clés libres: 19F NMR; Ensembles; Expression of GPCRs; Functional states; GPCR structure; GPCR-ligand interactions; Protein NMR
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 14 juill. 2021 15:57
Dernière modification: 15 févr. 2022 18:47
URI: https://espace.inrs.ca/id/eprint/11828

Actions (Identification requise)

Modifier la notice Modifier la notice