STERIC PRESENTATION AND RECOGNITION OF THE SACCHARIDE CHAINS OF GLYCOLIPIDS AT THE CELL-SURFACE - FAVORED CONFORMATIONS OF THE SACCHARIDE-LIPID LINKAGE CALCULATED USING MOLECULAR MECHANICS (MM3)

The orientation of the saccharide moiety of glycolipids at the membrane surface is determined by an interplay of different steric factors, e.g. the conformation of the saccharide chain, the conformation of the saccharide-lipid linkage and restrictions due to the membrane surface. In the present study the preferred conformations of the saccharide-lipid linkages of glucosylceramides with normal and hydroxy fatty acids and of glucosyldiglycerides with acyl and alkyl chains were studied using molecular mechanics (MM3). The populations of different conformers were calculated on the basis of relaxed energy maps. Calculations on glucosylceramides at a dielectric constant (epsilon) of 4 showed three dominating conformers: phi/psi/theta1 = +sc/ap/-sc (global energy minimum), +sc/-sc/ap and +sc/ap/ap, respectively. In sphingolipids the +sc rotamer of theta1 is disfavoured due to a Hassel-Ottar interaction involving the sphingosine O1 and O3 oxygen atoms. Alpha-OHydroxylation of the fatty acid does not significantly affect the conformational preferences of the saccharide-ceramide linkage at epsilon-values relevant for biomembranes. In glycoglycerolipids the global energy minimum is shifted to the phi/psi/theta1 = +sc/ap/ap conformation. For glycolipids located in membranes additional steric restrictions are imposed by the surrounding lipid layer. These restrictions in the steric presentation appear to be of crucial significance for the selective recognition and crypticity of glycolipids in membranes.