Characterization of protein-glycolipid recognition at the membrane bilayer.
A growing number of important molecular recognition events are being shown to involve the interactions between proteins and glycolipids. Glycolipids are molecules in which one or more monosaccharides are glycosidically linked to a lipid moiety. The lipid moiety is generally buried in the cell membrane or other bilayer, leaving the oligosaccharide moiety exposed but in close proximity to the bilayer surface. This presents a unique environment for protein-carbohydrate interactions, and studies to determine the influence of the bilayer on these phenomena are in their infancy. One important property of the bilayer is the ability to orient and cluster glycolipid species, as strong interactions in biological systems are often achieved through multivalency arising from the simultaneous association of two or more proteins and receptors. This is especially true of protein-carbohydrate binding because of the unusually low affinities that characterize the monovalent interactions. More recent studies have also shown that the composition of the lipid bilayer is a critical parameter in protein-glycolipid recognition. The fluidity of the bilayer allows for correct geometric positioning of the oligosaccharide head group relative to the binding sites on the protein. In addition, there are activity-based and structural data demonstrating the impact of the bilayer microenvironment on the modulation of oligosaccharide presentation. The use of model membranes in biosensor-based methods has supplied decisive evidence of the importance of the membrane in receptor presentation. These data can be correlated with three-dimensional structural information from X-ray crystallography, NMR, and molecular mechanics to provide insight into specific protein-carbohydrate inter--actions at the bilayer.
Department of Biochemistry, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada, K1H 8M5.
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Roger MacKenzie
D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use; D000937:Antigen-Antibody Reactions; D001427:Bacterial Toxins / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D002236:Carbohydrate Conformation; D050260:Carbohydrate Metabolism; D002240:Carbohydrate Sequence; D002241:Carbohydrates / Q000737:chemistry; D018360:Crystallography, X-Ray; D005732:Gangliosides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D006017:Glycolipids / Q000737:chemistry / Q000378:metabolism*; D006028:Glycosphingolipids / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes; D046911:Macromolecular Substances; D009682:Magnetic Resonance Spectroscopy; D008545:Melanoma / Q000628:therapy; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D022622:Shiga Toxin 1; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D020349:Surface Plasmon Resonance; D014281:Trihexosylceramides / Q000737:chemistry / Q000378:metabolism
D000911:Antibodies, Monoclonal; D001427:Bacterial Toxins; D002241:Carbohydrates; D005732:Gangliosides; D006017:Glycolipids; D006028:Glycosphingolipids; D008051:Lipid Bilayers; D008081:Liposomes; D046911:Macromolecular Substances; D008563:Membrane Lipids; D011506:Proteins; D022622:Shiga Toxin 1; D014281:Trihexosylceramides; C026226:ganglioside, GD3; C018549:globotriaosylceramide