Functional Solubilization of the β-adrenoceptor Using Diisobutylene Maleic Acid

Overview

Journal iScience

Publisher Cell Press

Date 2021 Nov 26

PMID 34825145

Citations 5

Authors

Clare R Harwood

David A Sykes

Bradley L Hoare

Franziska M Heydenreich

Romez Uddin

David R Poyner

Stephen J Briddon

D B Veprintsev

Affiliations

Soon will be listed here.

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 βAR in the polymer diisobutylene maleic acid (DIBMA). We demonstrate that βAR remains functional in the DIBMA lipid particle and shows improved thermal stability compared with the n-dodecyl-β-D-maltopyranoside detergent-solubilized βAR. This unique method of extracting βAR 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.

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