Journal Article

FZJ-2026-00400

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Capturing G protein-coupled receptors into native lipid-bilayer nanodiscs using new diisobutylene/maleic acid (DIBMA) copolymers

Chu, C. ; Vargas, C. ; Barbosa, M. C. ; Sommerhage, S.FZJ* ; Rechberger, G. N. ; Pahovnik, D. ; Žagar, E. ; Schröder, G. F.FZJ* ; Keller, S. (Corresponding author) ; Etzkorn, M. (Corresponding author)FZJ*

2025
Academic Press Orlando, Fla.

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Please use a persistent id in citations: doi:10.1016/j.ymeth.2025.08.013  doi:10.34734/FZJ-2026-00400

Abstract: Many membrane proteins, including G protein-coupled receptors (GPCRs), are susceptible to denaturation when extracted from their native membrane by detergents. Therefore, alternative methods have been developed, including amphiphilic copolymers that enable the direct extraction of functional membrane proteins along with their surrounding lipids. Among these amphiphilic copolymers, styrene/maleic acid (SMA) and diisobutylene/maleic acid (DIBMA) polymers have been extensively studied. Despite their many benefits, SMA and DIBMA polymers also have considerable drawbacks limiting their applications. Herein, we describe a series of new amphiphilic copolymers derived from DIBMA via partial amidation of the carboxylate pendant groups with various biocompatible amines. We characterize the new polymer’s nanodisc-forming properties and ability to extract the melanocortin 4 receptor (MC4R), a prototypical class A GPCR. While each new DIBMA variant displays features that may be favorable for selected applications, we identified a PEGylated DIBMA variant called mPEG4-DIBMA as particularly promising. In the tested system mPEG4-DIBMA abolishes unspecific interactions and outperforms other polymers by achieving higher extraction efficiencies of MC4R from Sf9 insect cell membranes. The new nanodisc-forming polymer combines two key advantages that are crucial for investigating GPCRs in a well-defined but still native lipid-bilayer environment, thus paving the way for manifold future applications.

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Contributing Institute(s):

1. Strukturbiologie (ER-C-3)

Research Program(s):

1. 5352 - Understanding the Functionality of Soft Matter and Biomolecular Systems (POF4-535) (POF4-535)
2. 5241 - Molecular Information Processing in Cellular Systems (POF4-524) (POF4-524)

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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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