A novel high-throughput screen for identifying lipids that stabilise membrane proteins in detergent based solution.

Membrane proteins have a range of crucial biological functions and are the target of about 60% of all prescribed drugs. For most studies, they need to be extracted out of the lipid-bilayer, e.g. by detergent solubilisation, leading to the loss of native lipids, which may disturb important protein-li...

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Autores principales: Cristina Cecchetti, Jannik Strauss, Claudia Stohrer, Claire Naylor, Edward Pryor, Jeanette Hobbs, Simon Tanley, Adrian Goldman, Bernadette Byrne
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Publicado: Public Library of Science (PLoS) 2021
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Acceso en línea:https://doaj.org/article/22e197f755e54af484c0e5dea3a85437
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spelling oai:doaj.org-article:22e197f755e54af484c0e5dea3a854372021-12-02T20:09:17ZA novel high-throughput screen for identifying lipids that stabilise membrane proteins in detergent based solution.1932-620310.1371/journal.pone.0254118https://doaj.org/article/22e197f755e54af484c0e5dea3a854372021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0254118https://doaj.org/toc/1932-6203Membrane proteins have a range of crucial biological functions and are the target of about 60% of all prescribed drugs. For most studies, they need to be extracted out of the lipid-bilayer, e.g. by detergent solubilisation, leading to the loss of native lipids, which may disturb important protein-lipid/bilayer interactions and thus functional and structural integrity. Relipidation of membrane proteins has proven extremely successful for studying challenging targets, but the identification of suitable lipids can be expensive and laborious. Therefore, we developed a screen to aid the high-throughput identification of beneficial lipids. The screen covers a large lipid space and was designed to be suitable for a range of stability assessment methods. Here, we demonstrate its use as a tool for identifying stabilising lipids for three membrane proteins: a bacterial pyrophosphatase (Tm-PPase), a fungal purine transporter (UapA) and a human GPCR (A2AR). A2AR is stabilised by cholesteryl hemisuccinate, a lipid well known to stabilise GPCRs, validating the approach. Additionally, our screen also identified a range of new lipids which stabilised our test proteins, providing a starting point for further investigation and demonstrating its value as a novel tool for membrane protein research. The pre-dispensed screen will be made commercially available to the scientific community in future and has a number of potential applications in the field.Cristina CecchettiJannik StraussClaudia StohrerClaire NaylorEdward PryorJeanette HobbsSimon TanleyAdrian GoldmanBernadette ByrnePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 7, p e0254118 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Cristina Cecchetti
Jannik Strauss
Claudia Stohrer
Claire Naylor
Edward Pryor
Jeanette Hobbs
Simon Tanley
Adrian Goldman
Bernadette Byrne
A novel high-throughput screen for identifying lipids that stabilise membrane proteins in detergent based solution.
description Membrane proteins have a range of crucial biological functions and are the target of about 60% of all prescribed drugs. For most studies, they need to be extracted out of the lipid-bilayer, e.g. by detergent solubilisation, leading to the loss of native lipids, which may disturb important protein-lipid/bilayer interactions and thus functional and structural integrity. Relipidation of membrane proteins has proven extremely successful for studying challenging targets, but the identification of suitable lipids can be expensive and laborious. Therefore, we developed a screen to aid the high-throughput identification of beneficial lipids. The screen covers a large lipid space and was designed to be suitable for a range of stability assessment methods. Here, we demonstrate its use as a tool for identifying stabilising lipids for three membrane proteins: a bacterial pyrophosphatase (Tm-PPase), a fungal purine transporter (UapA) and a human GPCR (A2AR). A2AR is stabilised by cholesteryl hemisuccinate, a lipid well known to stabilise GPCRs, validating the approach. Additionally, our screen also identified a range of new lipids which stabilised our test proteins, providing a starting point for further investigation and demonstrating its value as a novel tool for membrane protein research. The pre-dispensed screen will be made commercially available to the scientific community in future and has a number of potential applications in the field.
format article
author Cristina Cecchetti
Jannik Strauss
Claudia Stohrer
Claire Naylor
Edward Pryor
Jeanette Hobbs
Simon Tanley
Adrian Goldman
Bernadette Byrne
author_facet Cristina Cecchetti
Jannik Strauss
Claudia Stohrer
Claire Naylor
Edward Pryor
Jeanette Hobbs
Simon Tanley
Adrian Goldman
Bernadette Byrne
author_sort Cristina Cecchetti
title A novel high-throughput screen for identifying lipids that stabilise membrane proteins in detergent based solution.
title_short A novel high-throughput screen for identifying lipids that stabilise membrane proteins in detergent based solution.
title_full A novel high-throughput screen for identifying lipids that stabilise membrane proteins in detergent based solution.
title_fullStr A novel high-throughput screen for identifying lipids that stabilise membrane proteins in detergent based solution.
title_full_unstemmed A novel high-throughput screen for identifying lipids that stabilise membrane proteins in detergent based solution.
title_sort novel high-throughput screen for identifying lipids that stabilise membrane proteins in detergent based solution.
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/22e197f755e54af484c0e5dea3a85437
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