title: Isomeric Detergent Comparison for Membrane Protein Stability: Importance of Inter-Alkyl-Chain Distance and Alkyl Chain Length.
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 C12alkyl 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.
authors.affiliation: Department of Bionanotechnology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, 15588, Korea.
authors.forename: Kyung Ho
authors.identifier: http://orcid.org/0000-0001-6038-0816
authors.initials: KH
authors.lastname: Cho
authors.affiliation: Department of Cell Physiology and Molecular Biophysics, Center for Membrane Protein Research, School of Medicine, Texas Tech University Health Sciences Center, 3601 4thStreet MS 6551, Lubbock, TX, 79430, USA.
authors.forename: Parameswaran
authors.identifier: http://orcid.org/0000-0002-6020-1547
authors.initials: P
authors.lastname: Hariharan
authors.affiliation: Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3, 18.6 Panum Institute, 2200, Copenhagen, Denmark.
authors.forename: Jonas S
authors.identifier: http://orcid.org/0000-0002-6743-276X
authors.initials: JS
authors.lastname: Mortensen
authors.affiliation: Molecular and Cellular Physiology, Stanford University, 157 Beckman Center, 279 Campus Drive, Stanford, CA, 94305, USA.
authors.forename: Yang
authors.identifier: http://orcid.org/0000-0001-5115-0736
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3, 18.6 Panum Institute, 2200, Copenhagen, Denmark.
authors.forename: Anne K
authors.identifier: http://orcid.org/0000-0002-6627-3330
authors.initials: AK
authors.lastname: Nielsen
authors.affiliation: Department of Life Sciences, Imperial College London, Exhibition Road, South Kensington, London, SW7 2AZ, UK.
authors.forename: Bernadette
authors.identifier: http://orcid.org/0000-0001-9598-9832
authors.initials: B
authors.lastname: Byrne
authors.affiliation: Molecular and Cellular Physiology, Stanford University, 157 Beckman Center, 279 Campus Drive, Stanford, CA, 94305, USA.
authors.forename: Brian K
authors.identifier: http://orcid.org/0000-0001-5958-3990
authors.initials: BK
authors.lastname: Kobilka
authors.affiliation: Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3, 18.6 Panum Institute, 2200, Copenhagen, Denmark.
authors.forename: Claus J
authors.identifier: http://orcid.org/0000-0002-1773-1446
authors.initials: CJ
authors.lastname: Loland
authors.affiliation: Department of Cell Physiology and Molecular Biophysics, Center for Membrane Protein Research, School of Medicine, Texas Tech University Health Sciences Center, 3601 4thStreet MS 6551, Lubbock, TX, 79430, USA.
authors.forename: Lan
authors.identifier: http://orcid.org/0000-0002-2274-361X
authors.initials: L
authors.lastname: Guan
authors.affiliation: Department of Bionanotechnology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, 15588, Korea.
authors.forename: Pil Seok
authors.identifier: http://orcid.org/0000-0003-1799-3304
authors.initials: PS
authors.lastname: Chae
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D003902:Detergents / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D007536:Isomerism; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008823:Micelles; D055550:Protein Stability; D012486:Salmonella typhimurium / Q000201:enzymology; D012995:Solubility; D027981:Symporters / Q000737:chemistry / Q000378:metabolism; D013696:Temperature; D014992:Xylenes / Q000737:chemistry
chemical_list: D001426:Bacterial Proteins; D003902:Detergents; D008565:Membrane Proteins; D008823:Micelles; D027981:Symporters; D014992:Xylenes; C031286:4-xylene; C021548:melibiose permease
keywords: amphiphiles; detergents; membrane proteins; noncovalent interactions; protein solubilization; protein stabilization