A lipid matrix model of membrane raft structure.
Domains in cell membranes are created by lipid-lipid interactions and are referred to as membrane rafts. Reliable isolation methods have been developed which have shown that rafts from the same membranes have different proteins and can be sub-fractionated by immunoaffinity methods. Analysis of these raft subfractions shows that they are also comprised of different molecular species of lipids. The major lipid classes present are phospholipids, glycosphingolipids and cholesterol. Model studies show that mixtures of phospholipids, particularly sphingomyelin, and cholesterol form liquid-ordered phase with properties intermediate between a gel and fluid phase. This type of liquid-ordered phase dominates theories of domain formation and raft structure in biological membranes. Recently it has been shown that sphingolipids with long (22-26C) N-acyl fatty acids form quasi-crystalline bilayer structures with diacylphospholipids that have well-defined stoichiometries. A two tier heuristic model of membrane raft structure is proposed in which liquid-ordered phase created by a molecular complex between sphingolipids with hydrocarbon chains of approximately equal length and cholesterol acts as a primary staging area for selecting raft proteins. Tailoring of the lipid anchors of raft proteins takes place at this site. Assembly of lipid-anchored proteins on a scaffold of sphingolipids with asymmetric hydrocarbon chains and phospholipids arranged in a quasi-crystalline bilayer structure serves to concentrate and orient the proteins in a manner that couples them functionally within the membrane. Specificity is inherent in the quasi-crystalline lipid structure of liquid-ordered matrices formed by both types of complex into which protein lipid anchors are interpolated. An interaction between the sugar residues of the glycolipids and the raft proteins provides an additional level of specificity that distinguishes one raft from another.
Quinn
Peter J
PJ
Biochemistry Department, King's College London, 150 Stamford Street, London, UK. p.quinn@kcl.ac.uk
D000818:Animals; D002784:Cholesterol / Q000737:chemistry; D003902:Detergents / Q000737:chemistry; D006028:Glycosphingolipids / Q000737:chemistry; D006801:Humans; D008563:Membrane Lipids / Q000737:chemistry*; D021962:Membrane Microdomains / Q000737:chemistry* / Q000648:ultrastructure; D008954:Models, Biological; D010743:Phospholipids / Q000737:chemistry
D003902:Detergents; D006028:Glycosphingolipids; D008563:Membrane Lipids; D010743:Phospholipids; D002784:Cholesterol