@article{Yoon:2024:10.1021/acs.bioconjchem.3c00507,
author = {Yoon, S and Bae, HE and Hariharan, P and Nygaard, A and Lan, B and Woubshete, M and Sadaf, A and Liu, X and Loland, CJ and Byrne, B and Guan, L and Chae, PS},
doi = {10.1021/acs.bioconjchem.3c00507},
journal = {Bioconjugate Chemistry},
pages = {223--231},
title = {Rational approach to improve detergent efficacy for membrane protein stabilization},
url = {http://dx.doi.org/10.1021/acs.bioconjchem.3c00507},
volume = {35},
year = {2024}
}

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TY  - JOUR
AB  - 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.
AU  - Yoon,S
AU  - Bae,HE
AU  - Hariharan,P
AU  - Nygaard,A
AU  - Lan,B
AU  - Woubshete,M
AU  - Sadaf,A
AU  - Liu,X
AU  - Loland,CJ
AU  - Byrne,B
AU  - Guan,L
AU  - Chae,PS
DO  - 10.1021/acs.bioconjchem.3c00507
EP  - 231
PY  - 2024///
SN  - 1043-1802
SP  - 223
TI  - Rational approach to improve detergent efficacy for membrane protein stabilization
T2  - Bioconjugate Chemistry
UR  - http://dx.doi.org/10.1021/acs.bioconjchem.3c00507
UR  - https://www.ncbi.nlm.nih.gov/pubmed/38215010
UR  - https://pubs.acs.org/doi/10.1021/acs.bioconjchem.3c00507
UR  - http://hdl.handle.net/10044/1/109739
VL  - 35
ER  - 

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