title: Sphingolipid symmetry governs membrane lipid raft structure.
abstract: Lipid domain formation in membranes underlies the concept of rafts but their structure is controversial because the key role of cholesterol has been challenged. The configuration of glycosphingolipid receptors for agonists, bacterial toxins and enveloped viruses in plasma membrane rafts appears to be an important factor governing ligand binding and infectivity but the details are as yet unresolved. I have used X-ray diffraction methods to examine how cholesterol affects the distribution of glycosphingolipid in aqueous dispersions of an equimolar mixture of cholesterol and egg-sphingomyelin containing different proportions of glucosylceramide from human extracts. Three coexisting liquid-ordered bilayer structures are observed at 37°C in mixtures containing up to 20mol% glycosphingolipid. All the cholesterol was sequestered in one bilayer with the minimum amount of sphingomyelin (33mol%) to prevent formation of cholesterol crystals. The other two bilayers consisted of sphingomyelin and glucosylceramide. Asymmetric molecular species of glucosylceramide with N-acyl chains longer than 20 carbons form an equimolar complex with sphingomyelin in which the glycosidic residues are arranged in hexagonal array. Symmetric molecular species mix with sphingomyelin in proportions less than equimolar to form quasicrystalline bilayers. When the glycosphingolipid exceeds equimolar proportions with sphingomyelin cholesterol is incorporated into the structure and formation of a gel phase of glucosylceramide is prevented. The demonstration of particular structural features of ceramide molecular species combined with the diversity of sugar residues of glycosphingolipid classes paves the way for a rational approach to understanding the functional specificity of lipid rafts and how they are coupled across cell membranes.
authors.affiliation: Department of Biochemistry, King's College London, 150 Stamford Street, London SE1 9NH, UK. Electronic address: p.quinn@kcl.ac.uk.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Quinn
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002645:Chickens; D002784:Cholesterol / Q000378:metabolism; D004531:Eggs; D005963:Glucosylceramides / Q000378:metabolism; D006028:Glycosphingolipids / Q000378:metabolism; D006801:Humans; D008051:Lipid Bilayers / Q000378:metabolism*; D008563:Membrane Lipids / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism*; D013107:Sphingolipids / Q000378:metabolism*; D013109:Sphingomyelins / Q000378:metabolism
chemical_list: D005963:Glucosylceramides; D006028:Glycosphingolipids; D008051:Lipid Bilayers; D008563:Membrane Lipids; D013107:Sphingolipids; D013109:Sphingomyelins; D002784:Cholesterol
keywords: Cholesterol; Glycosphingolipid; Lipid bilayer structure; Membrane raft; Raft; Sphingomyelin