title: Accessible Mannitol-Based Amphiphiles (MNAs) for Membrane Protein Solubilisation and Stabilisation.
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 (β2 AR), 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 β2 AR. The ease of preparation together with the enhanced membrane protein stabilisation efficacy demonstrates the value of these agents for future membrane protein research.
authors.affiliation: Department of Bionanotechnology, Hanyang University, Ansan, 426-791, Korea.
authors.forename: Hazrat
authors.identifier: 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: 0000-0001-5115-0736
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Life Sciences, Imperial College London, London, SW7 2AZ, UK.
authors.forename: Nicola J
authors.identifier: 0000-0002-9198-4935
authors.initials: NJ
authors.lastname: Scull
authors.affiliation: Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, DK-2200, Denmark.
authors.forename: Jonas S
authors.identifier: 0000-0002-6743-276X
authors.initials: JS
authors.lastname: Mortensen
authors.affiliation: Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Jeffrey
authors.identifier: 0000-0001-5744-9018
authors.initials: J
authors.lastname: Tarrasch
authors.affiliation: Department of Bionanotechnology, Hanyang University, Ansan, 426-791, Korea.
authors.forename: Hyoung Eun
authors.identifier: 0000-0001-8302-2990
authors.initials: HE
authors.lastname: Bae
authors.affiliation: Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, DK-2200, Denmark.
authors.forename: Claus J
authors.identifier: 0000-0002-1773-1446
authors.initials: CJ
authors.lastname: Loland
authors.affiliation: Department of Life Sciences, Imperial College London, London, SW7 2AZ, UK.
authors.forename: Bernadette
authors.identifier: 0000-0001-9598-9832
authors.initials: B
authors.lastname: Byrne
authors.affiliation: Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Brian K
authors.identifier: 0000-0001-5958-3990
authors.initials: BK
authors.lastname: Kobilka
authors.affiliation: Department of Bionanotechnology, Hanyang University, Ansan, 426-791, Korea. pchae@hanyang.ac.kr.
authors.forename: Pil Seok
authors.identifier: 0000-0003-1799-3304
authors.initials: PS
authors.lastname: Chae
mesh_terms: D017920:Antiporters / Q000737:chemistry / Q000302:isolation & purification; D017360:Arabidopsis / Q000737:chemistry; D029681:Arabidopsis Proteins / Q000737:chemistry / Q000302:isolation & purification; D001426:Bacterial Proteins / Q000737:chemistry / Q000302:isolation & purification; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D045342:Light-Harvesting Protein Complexes / Q000737:chemistry / Q000302:isolation & purification; D008353:Mannitol / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry* / Q000302:isolation & purification; D055550:Protein Stability; D018343:Receptors, Adrenergic, beta-2 / Q000737:chemistry / Q000302:isolation & purification; D016354:Rhodobacter capsulatus / Q000737:chemistry; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry*
chemical_list: D017920:Antiporters; D029681:Arabidopsis Proteins; C469216:BOR1 protein, Arabidopsis; D001426:Bacterial Proteins; D045342:Light-Harvesting Protein Complexes; D008565:Membrane Proteins; D018343:Receptors, Adrenergic, beta-2; D013501:Surface-Active Agents; C094744:light-harvesting complex 1, Rhodospirillum; D008353:Mannitol
keywords: amphiphile design; electron microscopy; membrane proteins; novel detergents; protein stabilization