Functional solubilization of the β 2-adrenoceptor using diisobutylene maleic acid

Abstract

The β2-adrenoceptor (β2AR) is a well-established target in asthma and a prototypical G protein-coupled receptor for biophysical studies. Solubilization of membrane proteins has classically involved the use of detergents. However, the detergent environment differs from the native membrane environment and often destabilizes membrane proteins. Use of amphiphilic copolymers is a promising strategy to solubilize membrane proteins within their native lipid environment in the complete absence of detergents. Here we show the isolation of the β 2AR in the polymer diisobutylene maleic acid (DIBMA). We demonstrate that β 2AR remains functional in the DIBMA lipid particle and shows improved thermal stability compared with the n-dodecyl-β-D-maltopyranoside detergent-solubilized β 2AR. This unique method of extracting β 2AR offers significant advantages over previous methods routinely employed such as the introduction of thermostabilizing mutations and the use of detergents, particularly for functional biophysical studies.

Publication DOI: https://doi.org/10.1016/j.isci.2021.103362
Divisions: College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences
Additional Information: © 2021 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Funding: C.R.H. was funded by a Medical Research Council (MRC) IMPACT PhD studentship.
Uncontrolled Keywords: Biophysical chemistry,Membranes,Protein,General
Publication ISSN: 2589-0042
Last Modified: 14 May 2024 17:49
Date Deposited: 02 Nov 2021 15:33
Full Text Link:
Related URLs: https://www.sci ... 333X?via%3Dihub (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2021-12-17
Published Online Date: 2021-10-28
Accepted Date: 2021-10-25
Authors: Harwood, C.R.
Sykes, D.A.
Hoare, B.
Heydenreich, F.M.
Uddin, R.
Poyner, D.R. (ORCID Profile 0000-0003-1590-112X)
Briddon, S.J.
Veprintsev, D.B.

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