Isomeric Detergent Comparison for Membrane Protein Stability: Importance of Inter‐Alkyl‐Chain Distance and Alkyl Chain Length |
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| Authors: | Kyung Ho Cho Dr Parameswaran Hariharan Jonas S Mortensen Dr Yang Du Anne K Nielsen Dr Bernadette Byrne Prof Brian K Kobilka Prof Claus J Loland Prof Lan Guan Prof Pil Seok Chae |
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| Affiliation: | 1. Department of Bionanotechnology, Hanyang University, Sangnok-gu, Ansan, Korea;2. Department of Cell Physiology and Molecular Biophysics, Center for Membrane Protein Research, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA;3. Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark;4. Molecular and Cellular Physiology, Stanford University, Stanford, CA, USA;5. Department of Life Sciences, Imperial College London, South Kensington, London, UK |
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| Abstract: | Membrane proteins encapsulated by detergent micelles are widely used for structural study. Because of their amphipathic property, detergents have the ability to maintain protein solubility and stability in an aqueous medium. However, conventional detergents have serious limitations in their scope and utility, particularly for eukaryotic membrane proteins and membrane protein complexes. Thus, a number of new agents have been devised; some have made significant contributions to membrane protein structural studies. However, few detergent design principles are available. In this study, we prepared meta and ortho isomers of the previously reported para‐substituted xylene‐linked maltoside amphiphiles (XMAs), along with alkyl chain‐length variation. The isomeric XMAs were assessed with three membrane proteins, and the meta isomer with a C12 alkyl chain was most effective at maintaining solubility/stability of the membrane proteins. We propose that interplay between the hydrophile–lipophile balance (HLB) and alkyl chain length is of central importance for high detergent efficacy. In addition, differences in inter‐alkyl‐chain distance between the isomers influence the ability of the detergents to stabilise membrane proteins. |
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| Keywords: | amphiphiles detergents membrane proteins noncovalent interactions protein solubilization protein stabilization |
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