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@ARTICLE{Chu:1050648,
author = {Chu, Ci and Vargas, Carolyn and Barbosa, Maria Carolina and
Sommerhage, Simon and Rechberger, Gerald N. and Pahovnik,
David and Žagar, Ema and Schröder, Gunnar F. and Keller,
Sandro and Etzkorn, Manuel},
title = {{C}apturing {G} protein-coupled receptors into native
lipid-bilayer nanodiscs using new diisobutylene/maleic acid
({DIBMA}) copolymers},
journal = {Methods},
volume = {244},
issn = {1046-2023},
address = {Orlando, Fla.},
publisher = {Academic Press},
reportid = {FZJ-2026-00400},
pages = {55 - 64},
year = {2025},
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.},
cin = {ER-C-3},
ddc = {540},
cid = {I:(DE-Juel1)ER-C-3-20170113},
pnm = {5352 - Understanding the Functionality of Soft Matter and
Biomolecular Systems (POF4-535) / 5241 - Molecular
Information Processing in Cellular Systems (POF4-524)},
pid = {G:(DE-HGF)POF4-5352 / G:(DE-HGF)POF4-5241},
typ = {PUB:(DE-HGF)16},
doi = {10.1016/j.ymeth.2025.08.013},
url = {https://juser.fz-juelich.de/record/1050648},
}