Dataset Information

Asymmetric maltose neopentyl glycol amphiphiles for a membrane protein study: effect of detergent asymmetricity on protein stability.

ABSTRACT: Maintaining protein stability in an aqueous solution is a prerequisite for protein structural and functional studies, but conventional detergents have increasingly showed limited ability to maintain protein integrity. A representative novel agent, maltose neopentyl glycol-3 (MNG-3), has recently substantially contributed to membrane protein structural studies. Motivated by the popular use of this novel agent, we prepared asymmetric versions of MNG-3 and evaluated these agents with several membrane proteins including two G protein-coupled receptors in this study. We found that some new MNGs were significantly more effective than MNG-3 at preserving protein integrity in the long term, suggesting that these asymmetric MNGs will find a wide use in membrane protein studies. In addition, this is the first study addressing the favorable effect of detergent asymmetric nature on membrane protein stability.

SUBMITTER: Bae HE

PROVIDER: S-EPMC6346398 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Asymmetric maltose neopentyl glycol amphiphiles for a membrane protein study: effect of detergent asymmetricity on protein stability.

Bae Hyoung Eun HE Du Yang Y Hariharan Parameswaran P Mortensen Jonas S JS Kumar Kaavya K KK Ha Betty B Das Manabendra M Lee Hyun Sung HS Loland Claus J CJ Guan Lan L Kobilka Brian K BK Chae Pil Seok PS

Chemical science 20181105 4

Maintaining protein stability in an aqueous solution is a prerequisite for protein structural and functional studies, but conventional detergents have increasingly showed limited ability to maintain protein integrity. A representative novel agent, maltose neopentyl glycol-3 (MNG-3), has recently substantially contributed to membrane protein structural studies. Motivated by the popular use of this novel agent, we prepared asymmetric versions of MNG-3 and evaluated these agents with several membra ...[more]

PMID: 30774908

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Project description:Glucoside detergents are successfully used for membrane protein crystallization mainly because of their ability to form small protein-detergent complexes. In a previous study, we introduced glucose neopentyl glycol (GNG) amphiphiles with a branched diglucoside structure that has facilitated high resolution crystallographic structure determination of several membrane proteins. Like other glucoside detergents, however, these GNGs were less successful than DDM in stabilizing membrane proteins, limiting their wide use in protein structural study. As a strategy to improve GNG efficacy for protein stabilization, we introduced two different alkyl chains (i.e., main and pendant chains) into the GNG scaffold while maintaining the branched diglucoside head group. Of these pendant-bearing GNGs (P-GNGs), three detergents (GNG-2,14, GNG-3,13 and GNG-3,14) were not only notably better than both DDM (a gold standard detergent) and the previously described GNGs at stabilizing all six membrane proteins tested here, but were also as efficient as DDM at membrane protein extraction. The results suggest that the C14 main chain of the P-GNGs is highly compatible with the hydrophobic widths of membrane proteins, while the C2/C3 pendant chain is effective at strengthening detergent hydrophobic interactions. Based on the marked effect on protein stability and solubility, these glucoside detergents hold significant potential for membrane protein structural study. Furthermore, the independent roles of the detergent two alkyl chains first introduced in this study have shed light on new amphiphile design for membrane protein study. STATEMENT OF SIGNIFICANCE: Detergent efficacy for protein stabilization tends to be protein-specific, thus it is challenging to find a detergent that is effective at stabilizing multiple membrane proteins. By incorporating a pendant chain into our previous GNG scaffold, we prepared pendant chain-bearing GNGs (P-GNGs) and identified three P-GNGs that were highly effective at stabilizing all membrane proteins tested here including two GPCRs. In addition, the new detergents were as efficient as DDM at extracting membrane proteins, enabling use of these detergents over the multiple steps of protein isolation. The key difference between the P-GNGs and other glucoside detergents, the presence of a pendant chain, is likely to be responsible for their markedly enhanced protein stabilization behavior.

Dataset Information

Asymmetric maltose neopentyl glycol amphiphiles for a membrane protein study: effect of detergent asymmetricity on protein stability.

Publications

Asymmetric maltose neopentyl glycol amphiphiles for a membrane protein study: effect of detergent asymmetricity on protein stability.

Similar Datasets

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