Glyco-Steroidal Amphiphiles (GSAs) for membrane protein structural study
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
Integral membrane proteins pose considerable challenges to high resolution structural analysis. Maintaining membrane proteins in their native state during protein isolation is essential for structural study of these bio-macromolecules. Detergents are the most commonly used amphiphilic compounds for stabilizing membrane proteins in solution outside a lipid bilayer. We previously introduced a glyco-diosgenin (GDN) detergent that was shown to be highly effective at stabilizing a wide range of membrane proteins. This steroidal detergent has additionally gained attention due to its compatibility with membrane protein structure study via cryo-EM. However, synthetic inconvenience limits widespread use of GDN in membrane protein study. To improve its synthetic accessibility and to further enhance detergent efficacy for protein stabilization, we designed a new class of glyco-steroid-based detergents using three steroid units: cholestanol, cholesterol and diosgenin. These new detergents were efficiently prepared and showed marked efficacy for protein stabilization in evaluation with a few model membrane proteins including two G protein-coupled receptors. Some new agents were not only superior to a gold standard detergent, DDM (n-dodecyl-β-d-maltoside), but were also more effective than the original GDN at preserving protein integrity long term. These agents represent valuable alternatives to GDN, and are likely to facilitate structural determination of challenging membrane proteins.
Date Issued
2022-04-05
Date Acceptance
2022-02-05
Citation
ChemBioChem: a European journal of chemical biology, 2022, 23 (7), pp.1-8
ISSN
1439-4227
Publisher
Wiley-VCH Verlag
Start Page
1
End Page
8
Journal / Book Title
ChemBioChem: a European journal of chemical biology
Volume
23
Issue
7
Copyright Statement
© 2022 Wiley-VCH GmbH. This is the peer reviewed version of the following article, which has been published in final form at https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cbic.202200027. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/35129249
Subjects
detergent design
detergent-detergent interactions
glyco-steroids
glycolipids
protein stabilization
Publication Status
Published
Coverage Spatial
Germany
Article Number
ARTN e202200027
Date Publish Online
2022-02-07