Functional GPCR expression in eukaryotic LEXSY system-Reference-Cited by-同舟云学术

Functional GPCR expression in eukaryotic LEXSY system

Published:2023-05-05 Issue: Volume: Page:
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Luginina Aleksandra^ORCID,Maslov Ivan^ORCID,Khorn Polina^ORCID,Volkov Oleksandr^ORCID,Khnykin Andrey^ORCID,Kuzmichev Pavel^ORCID,Shevtsov Mikhail^ORCID,Belousov Anatoliy^ORCID,Dashevskii Dmitrii^ORCID,Kornilov Daniil^ORCID,Bestsennaia Ekaterina^ORCID,Hofkens Johan^ORCID,Hendrix Jelle^ORCID,Gensch Thomas,Cherezov Vadim^ORCID,Ivanovich Valentin,Mishin Alexey^ORCID,Borshchevskiy Valentin^ORCID

Abstract

AbstractG protein-coupled receptors (GPCRs) represent an important class of drug targets, and their structural studies facilitate rational drug discovery. However, atomic structures of only about 20% of human GPCRs have been solved to date. Recombinant production of GPCRs for structural studies at a large scale is challenging due to their low expression levels and stability. Here we tested the eukaryotic system LEXSY (Leishmania tarentolae) for GPCR production. We expressed the human A2Aadenosine receptor (A2AAR) in LEXSY, purified it, and compared with the same receptor produced in insect cells, which is the most popular expression system for structural studies of GPCRs. The A2AAR purified from both expression systems showed similar purity, stability, ligand-induced conformational changes and structural dynamics, with a remarkably higher protein yield in the case of LEXSY expression.

Publisher

Cold Spring Harbor Laboratory

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