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Chemistry. 2019 Sep 2;25(49):11545-11554. doi: 10.1002/chem.201902468. Epub 2019 Aug 5.

Self-Assembly Behavior and Application of Terphenyl-Cored Trimaltosides for Membrane-Protein Studies: Impact of Detergent Hydrophobic Group Geometry on Protein Stability.

Author information

1
Department of Bionanotechnology, Hanyang University, Ansan, 15588, Korea.
2
Current address: Department of Chemistry, Mirpur University of Science & Technology, Mirpur, AJK, 10250, Pakistan).
3
Molecular and Cellular Physiology, Stanford, CA, 94305, USA.
4
Department of Neuroscience, University of Copenhagen, 2200, Copenhagen, Denmark.
5
Department of Cell Physiology and Molecular Biophysics, Center for Membrane Protein Research, School of Medicine, Texas Tech University Health Sciences Center Lubbock, TX, 79430, USA.
6
Molecular and Cellular Physiology and Structural Biology, Stanford University, Stanford, CA, 94305, USA.
7
Molecular Biophysics, Technische Universität Kaiserslautern (TUK), Erwin-Schrödinger-Str. 13, 67663, Kaiserslautern, Germany.
8
Department of Life Sciences, Imperial College London, London, SW7 2AZ, UK.

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.

KEYWORDS:

amphiphiles; glycolipids; membrane proteins; pi-interactions; self-assembly

PMID:
31243822
DOI:
10.1002/chem.201902468

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