Role of a-hydroxylation

The presence of an alpha-OH group in the acyl chain of the ceramide backbone of GalCer allows the formation of a H-bond network which orientates the galactose ring of GalCer so that the molecule adopts a typical L-shape structure (8). Consequently, the sugar head of the glycosphingolipid is available for a stacking interaction with exogenous ligands. In contrast, the galactose ring of GalCer containing a nonhydroxylated acyl chain protrudes at 180° with respect to the plane of the membrane. For this reason, microbial adhesins and/or toxins often recognize alpha-hydroxylated vs. nonhydroxylated galactose-containing glycosphingolipids (9-13) : e.g. HIV1 surface envelope glycoprotein gp120, infectious prion rods and Helicobacter pylori adhesins.