title: Resorcinarene-Based Facial Glycosides: Implication of Detergent Flexibility on Membrane-Protein Stability.
abstract: As a membrane-mimetic system, detergent micelles are popularly used to extract membrane proteins from lipid environments and to maintain their solubility and stability in an aqueous medium. However, many membrane proteins encapsulated in conventional detergents tend to undergo structural degradation during extraction and purification, thus necessitating the development of new agents with enhanced properties. In the current study, two classes of new amphiphiles are introduced, resorcinarene-based glucoside and maltoside amphiphiles (designated RGAs and RMAs, respectively), for which the alkyl chains are facially segregated from the carbohydrate head groups. Of these facial amphiphiles, two RGAs (RGA-C11 and RGA-C13) conferred markedly enhanced stability to four tested membrane proteins compared to a gold-standard conventional detergent. The relatively high water solubility and micellar stability of the RGAs compared to the RMAs, along with their generally favourable behaviours for membrane protein stabilisation described here, are likely to be, at least in part, a result of the high conformational flexibility of these glucosides. This study suggests that flexibility could be an important factor in determining the suitability of new detergents for membrane protein studies.
authors.affiliation: Department of Bionanotechnology, Hanyang University, Ansan, 155-88, Korea.
authors.forename: Hazrat
authors.identifier: http://orcid.org/0000-0002-5449-7660
authors.initials: H
authors.lastname: Hussain
authors.affiliation: Molecular and Cellular Physiology, Stanford University, 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 Cell Physiology and Molecular Biophysics, Center for Membrane Protein Research, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, 79430, USA.
authors.forename: Elena
authors.identifier: http://orcid.org/0000-0002-7892-9173
authors.initials: E
authors.lastname: Tikhonova
authors.affiliation: Center of Neuroscience, University of Copenhagen, Copenhagen, 2200, Denmark.
authors.forename: Jonas S
authors.identifier: http://orcid.org/0000-0002-6743-276X
authors.initials: JS
authors.lastname: Mortensen
authors.affiliation: Department of Life Sciences, Imperial College London, London, SW7 2AZ, UK.
authors.forename: Orquidea
authors.identifier: http://orcid.org/0000-0003-0746-6666
authors.initials: O
authors.lastname: Ribeiro
authors.affiliation: 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.
authors.forename: Claudia
authors.identifier: http://orcid.org/0000-0003-4803-4077
authors.initials: C
authors.lastname: Santillan
authors.affiliation: Department of Bionanotechnology, Hanyang University, Ansan, 155-88, Korea.
authors.forename: Manabendra
authors.identifier: http://orcid.org/0000-0003-3690-3183
authors.initials: M
authors.lastname: Das
authors.affiliation: Department of Bionanotechnology, Hanyang University, Ansan, 155-88, Korea.
authors.forename: Muhammad
authors.identifier: http://orcid.org/0000-0002-4723-7924
authors.initials: M
authors.lastname: Ehsan
authors.affiliation: Center of Neuroscience, University of Copenhagen, Copenhagen, 2200, 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, Lubbock, TX, 79430, USA.
authors.forename: Lan
authors.identifier: http://orcid.org/0000-0002-2274-361X
authors.initials: L
authors.lastname: Guan
authors.affiliation: Molecular and Cellular Physiology, Stanford University, 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 Life Sciences, Imperial College London, London, SW7 2AZ, UK.
authors.forename: Bernadette
authors.identifier: http://orcid.org/0000-0001-9598-9832
authors.initials: B
authors.lastname: Byrne
authors.affiliation: Department of Bionanotechnology, Hanyang University, Ansan, 155-88, Korea.
authors.forename: Pil Seok
authors.identifier: http://orcid.org/0000-0003-1799-3304
authors.initials: PS
authors.lastname: Chae
mesh_terms: D001233:Aspergillus nidulans / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D047250:Calixarenes / Q000737:chemistry*; D003374:Coumarins / Q000737:chemistry; D003902:Detergents / Q000737:chemistry*; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism; D006027:Glycosides / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000737:chemistry; D011489:Protein Denaturation; D055550:Protein Stability; D012486:Salmonella typhimurium / Q000201:enzymology; D027981:Symporters / Q000737:chemistry / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D003374:Coumarins; D003902:Detergents; D005656:Fungal Proteins; D006027:Glycosides; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D027981:Symporters; C083852:UAPA protein, Aspergillus nidulans; C466160:resorcinarene; D047250:Calixarenes; D010649:Phenylalanine; C030860:N-(4-(7-diethylamino-4-methylcoumarin-3-yl)phenyl)maleimide; C021548:melibiose permease
keywords: facial amphiphiles; membrane proteins; molecular design; protein stability; resorcinarene glycosides