Rational approach to improve detergent efficacy for membrane protein stabilization
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
Membrane protein structures are essential for the molecular understanding of diverse cellular processes and drug discovery. Detergents are not only widely used to extract membrane proteins from membranes but also utilized to preserve native protein structures in aqueous solution. However, micelles formed by conventional detergents are suboptimal for membrane protein stabilization, necessitating the development of novel amphiphilic molecules with enhanced protein stabilization efficacy. In this study, we prepared two sets of tandem malonate-derived glucoside (TMG) variants, both of which were designed to increase the alkyl chain density in micelle interiors. The alkyl chain density was modulated either by reducing the spacer length (TMG-Ms) or by introducing an additional alkyl chain between the two alkyl chains of the original TMGs (TMG-Ps). When evaluated with a few membrane proteins including a G protein-coupled receptor, TMG-P10,8 was found to be substantially more efficient at extracting membrane proteins and also effective at preserving protein integrity in the long term compared to the previously described TMG-A13. This result reveals that inserting an additional alkyl chain between the two existing alkyl chains is an effective way to optimize detergent properties for membrane protein study. This new biochemical tool and the design principle described have the potential to facilitate membrane protein structure determination.
Date Issued
2024-02-21
Date Acceptance
2023-12-27
Citation
Bioconjugate Chemistry, 2024, 35 (2), pp.223-231
ISSN
1043-1802
Publisher
American Chemical Society
Start Page
223
End Page
231
Journal / Book Title
Bioconjugate Chemistry
Volume
35
Issue
2
Copyright Statement
Copyright © 2024 American Chemical Society. This document is the Accepted Manuscript version of a Published Work that appeared in final form in Bioconjugate Chem, after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.bioconjchem.3c00507
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/38215010
Subjects
Detergents
Membrane Proteins
Micelles
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2024-01-12