title: Conformationally Preorganized Diastereomeric Norbornane-Based Maltosides for Membrane Protein Study: Implications of Detergent Kink for Micellar Properties.
abstract: Detergents are essential tools for functional and structural studies of membrane proteins. However, conventional detergents are limited in their scope and utility, particularly for eukaryotic membrane proteins. Thus, there are major efforts to develop new amphipathic agents with enhanced properties. Here, a novel class of diastereomeric agents with a preorganized conformation, designated norbornane-based maltosides (NBMs), were prepared and evaluated for their ability to solubilize and stabilize membrane proteins. Representative NBMs displayed enhanced behaviors compared to n-dodecyl-β-d-maltoside (DDM) for all membrane proteins tested. Efficacy of the individual NBMs varied depending on the overall detergent shape and alkyl chain length. Specifically, NBMs with no kink in the lipophilic region conferred greater stability to the proteins than NBMs with a kink. In addition, long alkyl chain NBMs were generally better at stabilizing membrane proteins than short alkyl chain agents. Furthermore, use of one well-behaving NBM enabled us to attain a marked stabilization and clear visualization of a challenging membrane protein complex using electron microscopy. Thus, this study not only describes novel maltoside detergents with enhanced protein-stabilizing properties but also suggests that overall detergent geometry has an important role in determining membrane protein stability. Notably, this is the first systematic study on the effect of detergent kinking on micellar properties and associated membrane protein stability.
authors.affiliation: Department of Bionanotechnology, Hanyang University , Ansan 155-88, Korea.
authors.forename: Manabendra
authors.initials: M
authors.lastname: Das
authors.affiliation: Department of Molecular and Cellular Physiology, Stanford University , Stanford, California 94305, United States.
authors.forename: Yang
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Life Sciences, Imperial College London , London SW7 2AZ, United Kingdom.
authors.forename: Orquidea
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, Texas 79430, United States.
authors.forename: Parameswaran
authors.initials: P
authors.lastname: Hariharan
authors.affiliation: Department of Neuroscience and Pharmacology, University of Copenhagen , Copenhagen DK-2200, Denmark.
authors.forename: Jonas S
authors.initials: JS
authors.lastname: Mortensen
authors.affiliation: Life Sciences Institute, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Dhabaleswar
authors.initials: D
authors.lastname: Patra
authors.affiliation: Life Sciences Institute, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Georgios
authors.initials: G
authors.lastname: Skiniotis
authors.affiliation: Department of Neuroscience and Pharmacology, University of Copenhagen , Copenhagen DK-2200, Denmark.
authors.forename: Claus J
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, Texas 79430, United States.
authors.forename: Lan
authors.initials: L
authors.lastname: Guan
authors.affiliation: Department of Molecular and Cellular Physiology, Stanford University , Stanford, California 94305, United States.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Kobilka
authors.affiliation: Department of Life Sciences, Imperial College London , London SW7 2AZ, United Kingdom.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Byrne
authors.affiliation: Department of Bionanotechnology, Hanyang University , Ansan 155-88, Korea.
authors.forename: Pil Seok
authors.identifier: 0000-0003-1799-3304
authors.initials: PS
authors.lastname: Chae