Journal Article

FZJ-2024-00703

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Functional GPCR Expression in Eukaryotic LEXSY System

Luginina, A. ; Maslov, I. ; Khorn, P. ; Volkov, O. ; Khnykin, A. ; Kuzmichev, P. ; Shevtsov, M. ; Belousov, A. ; Kapranov, I. ; Dashevskii, D. ; Kornilov, D. ; Bestsennaia, E.FZJ* ; Hofkens, J. ; Hendrix, J. ; Gensch, T.FZJ* ; Cherezov, V. ; Ivanovich, V. ; Mishin, A. ; Borshchevskiy, V. (Corresponding author)

2023
Elsevier Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.jmb.2023.168310

Abstract: G protein-coupled receptors (GPCRs) form the largest superfamily of membrane proteins in the humangenome, and represent one of the most important classes of drug targets. Their structural studies facilitaterational drug discovery. However, atomic structures of only about 20% of human GPCRs have beensolved to date. Recombinant production of GPCRs for structural studies at a large scale is challengingdue to their low expression levels and stability. Therefore, in this study, we explored the efficacy of theeukaryotic system LEXSY (Leishmania tarentolae) for GPCR production. We selected the human A2Aadenosine receptor (A2AAR), as a model protein, expressed it in LEXSY, purified it, and compared withthe same receptor produced in insect cells, which is the most popular expression system for structuralstudies 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 yieldin the case of LEXSY expression. Overall, our results suggest that LEXSY is a promising platform forlarge-scale production of GPCRs for structural studies

Note: This work is supported by RSCF research grant22-74-00024 (https://rscf.ru/en/project/22-74-00024/). J. Ho. acknowledges support from theFlemish government through long-term structuralfunding Methusalem (CASAS2, Meth/15/04). J.He acknowledges the Research FoundationFlanders (FWO grants G0B9922N).

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Contributing Institute(s):

1. Molekular- und Zellphysiologie (IBI-1)

Research Program(s):

1. 5241 - Molecular Information Processing in Cellular Systems (POF4-524) (POF4-524)

Appears in the scientific report 2024

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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