Accessible Mannitol‐Based Amphiphiles (MNAs) for Membrane Protein Solubilisation and Stabilisation |
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| Authors: | Hazrat Hussain Dr Yang Du Nicola J Scull Jonas S Mortensen Jeffrey Tarrasch Hyoung Eun Bae Prof Claus J Loland Dr Bernadette Byrne Prof Brian K Kobilka Prof Pil Seok Chae |
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| Institution: | 1. Department of Bionanotechnology, Hanyang University, Ansan, Korea;2. Molecular and Cellular Physiology, Stanford University, Stanford, USA;3. Department of Life Sciences, Imperial College London, London, UK;4. Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark;5. Life Sciences Institute, University of Michigan, Ann Arbor, USA |
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| 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. |
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| Keywords: | amphiphile design electron microscopy membrane proteins novel detergents protein stabilization |
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