Rational Approach to Improve Detergent Efficacy for Membrane Protein Stabilization
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Rational Approach to Improve Detergent Efficacy for Membrane Protein Stabilization. / Yoon, Soyoung; Bae, Hyoung Eun; Hariharan, Parameswaran; Nygaard, Andreas; Lan, Baoliang; Woubshete, Menebere; Sadaf, Aiman; Liu, Xiangyu; Loland, Claus J.; Byrne, Bernadette; Guan, Lan; Chae, Pil Seok.
In: Bioconjugate Chemistry, Vol. 35, No. 2, 2024, p. 223–231.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Rational Approach to Improve Detergent Efficacy for Membrane Protein Stabilization
AU - Yoon, Soyoung
AU - Bae, Hyoung Eun
AU - Hariharan, Parameswaran
AU - Nygaard, Andreas
AU - Lan, Baoliang
AU - Woubshete, Menebere
AU - Sadaf, Aiman
AU - Liu, Xiangyu
AU - Loland, Claus J.
AU - Byrne, Bernadette
AU - Guan, Lan
AU - Chae, Pil Seok
N1 - Publisher Copyright: © 2024 American Chemical Society.
PY - 2024
Y1 - 2024
N2 - 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.
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.
U2 - 10.1021/acs.bioconjchem.3c00507
DO - 10.1021/acs.bioconjchem.3c00507
M3 - Journal article
C2 - 38215010
AN - SCOPUS:85182577278
VL - 35
SP - 223
EP - 231
JO - Bioconjugate Chemistry
JF - Bioconjugate Chemistry
SN - 1043-1802
IS - 2
ER -
ID: 384026024