Accessible Mannitol-Based Amphiphiles (MNAs) for Membrane Protein Solubilisation and Stabilisation

Hazrat Hussain, Yang Du, Nicola J. Scull, Jonas S. Mortensen, Jeffrey Tarrasch, Hyoung Eun Bae, Claus J. Loland, Bernadette Byrne, Brian K. Kobilka, Pil Seok Chae

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41 Citations (Scopus)

Abstract

Integral membrane proteins are amphipathic molecules crucial for all cellular life. The structural study of these macromolecules starts with protein extraction from the native membranes, followed by purification and crystallisation. Detergents are essential tools for these processes, but detergent-solubilised membrane proteins often denature and aggregate, resulting in loss of both structure and function. In this study, a novel class of agents, designated mannitol-based amphiphiles (MNAs), were prepared and characterised for their ability to solubilise and stabilise membrane proteins. Some of MNAs conferred enhanced stability to four membrane proteins including a G protein-coupled receptor (GPCR), the β2 adrenergic receptor (β2AR), compared to both n-dodecyl-d-maltoside (DDM) and the other MNAs. These agents were also better than DDM for electron microscopy analysis of the β2AR. The ease of preparation together with the enhanced membrane protein stabilisation efficacy demonstrates the value of these agents for future membrane protein research.
Original languageEnglish
JournalChemistry: A European Journal
Volume22
Issue number21
Pages (from-to)7068-7073
Number of pages6
ISSN0947-6539
DOIs
Publication statusPublished - 17 May 2016

Keywords

  • amphiphile design
  • electron microscopy
  • membrane proteins
  • novel detergents
  • protein stabilization

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