Bicelles Rich in Both Sphingolipids and Cholesterol and Their Use in Studies of Membrane Proteins

Overview

Journal J Am Chem Soc

Publisher American Chemical Society

Specialty Chemistry

Date 2020 Jun 25

PMID 32575981

Citations 20

Authors

James M Hutchison

Kuo-Chih Shih

Holger A Scheidt

Sarah M Fantin

Kristine F Parson

George A Pantelopulos

Haley R Harrington

Kathleen F Mittendorf

Shuo Qian

Richard A Stein

Scott E Collier

Melissa G Chambers

John Katsaras

Markus W Voehler

Brandon T Ruotolo

Daniel Huster

Robert L McFeeters

John E Straub

Mu-Ping Nieh

Charles R Sanders

Affiliations

Soon will be listed here.

Abstract

How the distinctive lipid composition of mammalian plasma membranes impacts membrane protein structure is largely unexplored, partly because of the dearth of isotropic model membrane systems that contain abundant sphingolipids and cholesterol. This gap is addressed by showing that phingomyelin and hlesterol-ich (SCOR) lipid mixtures with phosphatidylcholine can be cosolubilized by -dodecyl-β-melibioside to form bicelles. Small-angle X-ray and neutron scattering, as well as cryo-electron microscopy, demonstrate that these assemblies are stable over a wide range of conditions and exhibit the bilayered-disc morphology of ideal bicelles even at low lipid-to-detergent mole ratios. SCOR bicelles are shown to be compatible with a wide array of experimental techniques, as applied to the transmembrane human amyloid precursor C99 protein in this medium. These studies reveal an equilibrium between low-order oligomer structures that differ significantly from previous experimental structures of C99, providing an example of how ordered membranes alter membrane protein structure.

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