Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Mar;78(1):31-37.
doi: 10.1007/s10858-023-00430-7. Epub 2023 Dec 10.

19F-NMR studies of the impact of different detergents and nanodiscs on the A2A adenosine receptor

Francisco Mendoza-Hoffmann #  1   2 , Canyong Guo #  1   3 , Yanzhuo Song #  1   4 , Dandan Feng  1   3 , Lingyun Yang  1 , Kurt Wüthrich  5   6   7
Affiliations

19F-NMR studies of the impact of different detergents and nanodiscs on the A2A adenosine receptor

Francisco Mendoza-Hoffmann et al. J Biomol NMR. 2024 Mar.

Abstract

For the A2A adenosine receptor (A2AAR), a class A G-protein-coupled receptor (GPCR), reconstituted in n-dodecyl-β-D-maltoside (DDM)/‌‌‌‌‌cholesteryl hemisuccinate (CHS) mixed micelles, previous 19F-NMR studies revealed the presence of multiple simultaneously populated conformational states. Here, we study the influence of a different detergent, lauryl maltose neopentyl glycol (LMNG) in mixed micelles with CHS, and of lipid bilayer nanodiscs on these conformational equilibria. The populations of locally different substates are pronouncedly different in DDM/‌‌‌‌‌CHS and LMNG/‌‌‌‌‌CHS micelles, whereas the A2AAR conformational manifold in LMNG/‌‌‌‌‌CHS micelles is closely similar to that in the lipid bilayer nanodiscs. Considering that nanodiscs represent a closer match of the natural lipid bilayer membrane, these observations support that LMNG/‌‌‌‌‌CHS micelles are a good choice for reconstitution trials of class A GPCRs for NMR studies in solution.

Keywords: DDM/CHS micelles; G protein-coupled receptor; GPCR; LMNG/CHS micelles; Lipid nanodiscs; Membrane mimetics.

PubMed Disclaimer

References

    1. Chae PS, Rasmussen SG, Rana RR, Gotfryd K, Chandra R, Goren MA, Kruse AC, Nurva S, Loland CJ, Pierre Y, Drew D, Popot JL, Picot D, Fox BG, Guan L, Gether U, Byrne B, Kobilka B, Gellman SH (2010) Maltose-neopentyl glycol (MNG) amphiphiles for solubilization, stabilization and crystallization of membrane proteins. Nat Methods 7:1003–1008 - DOI
    1. Chung KY, Kim TH, Manglik A, Alvares R, Kobilka BK, Prosser RS (2012) Role of detergents in conformational exchange of a G protein-coupled receptor. J Biol Chem 287:36305–36311 - DOI
    1. Eddy MT, Lee MY, Gao ZG, White KL, Didenko T, Horst R, Audet M, Stanczak P, McClary KM, Han GW, Jacobson KA, Stevens RC, Wüthrich K (2018) Allosteric coupling of drug binding and intracellular signaling in the A2A adenosine receptor. Cell 172:68–80 - DOI
    1. Feng D, Feng G, Song Y, Wüthrich K (2023) Solvent accessibility of a GPCR transmembrane domain probed by in-membrane chemical modification (IMCM). FEBS Lett 597:1541–1549 - DOI
    1. Gallagher JR, Kim AJ, Gulati NM, Harris AK (2019) Negative-stain transmission electron microscopy of molecular complexes for image analysis by 2D class averaging. Curr Protoc Microbiol 54:e90 - DOI

MeSH terms

LinkOut - more resources