Self-assembly behavior and application of terphenyl-cored trimaltosides for membrane-protein studies: impact of detergent hydrophobic group geometry on protein stability
File(s)TPM_ms_revised BB.docx (2.58 MB)
Accepted version
Author(s)
Type
Journal Article
Abstract
Amphipathic agents are widely used in various fields including biomedical sciences. Micelle-forming detergents are particularly useful for in vitro membrane-protein characterization. As many conventional detergents are limited in their ability to stabilize membrane proteins, it is necessary to develop novel detergents to facilitate membrane-protein research. In the current study, we developed novel trimaltoside detergents with an alkyl pendant-bearing terphenyl unit as a hydrophobic group, designated terphenyl-cored maltosides (TPMs). We found that the geometry of the detergent hydrophobic group substantially impacts detergent self-assembly behavior, as well as detergent efficacy for membrane-protein stabilization. TPM-Vs, with a bent terphenyl group, were superior to the linear counterparts (TPM-Ls) at stabilizing multiple membrane proteins. The favorable protein stabilization efficacy of these bent TPMs is likely associated with a binding mode with membrane proteins distinct from conventional detergents and facial amphiphiles. When compared to n-dodecyl-β-d-maltoside (DDM), most TPMs were superior or comparable to this gold standard detergent at stabilizing membrane proteins. Notably, TPM-L3 was particularly effective at stabilizing the human β2 adrenergic receptor (β2 AR), a G-protein coupled receptor, and its complex with Gs protein. Thus, the current study not only provides novel detergent tools that are useful for membrane-protein study, but also suggests a critical role for detergent hydrophobic group geometry in governing detergent efficacy.
Date Issued
2019-09-02
Date Acceptance
2019-06-01
Citation
Chemistry - A European Journal, 2019, 25 (49), pp.11545-11554
ISSN
0947-6539
Publisher
Wiley
Start Page
11545
End Page
11554
Journal / Book Title
Chemistry - A European Journal
Volume
25
Issue
49
Copyright Statement
© 2019 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim. This is the accepted version of the following article: Ehsan, M. , Du, Y. , Mortensen, J. S., Hariharan, P. , Qu, Q. , Ghani, L. , Das, M. , Grethen, A. , Byrne, B. , Skiniotis, G. , Keller, S. , Loland, C. J., Guan, L. , Kobilka, B. K. and Chae, P. S. (2019), Self‐Assembly Behavior and Application of Terphenyl‐Cored Trimaltosides for Membrane‐Protein Studies: Impact of Detergent Hydrophobic Group Geometry on Protein Stability. Chem. Eur. J., which has been published in final form at https://doi.org/10.1002/chem.201902468
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/31243822
Subjects
amphiphiles
glycolipids
membrane proteins
pi-interactions
self-assembly
Publication Status
Published
Coverage Spatial
Germany
Date Publish Online
2019-06-26