Globotriaosyl ceramide receptor function – Where membrane structure and pathology intersect

The glycosphingolipid globotriaosyl ceramide, (Galα1-4Galß1-4 glucosyl ceramide-Gb3) also known as CD77 and the Pk blood group antigen, is bound by both verotoxins and by the HIV adhesin, gp120. Gb3 plays an important receptor role in VT induced hemolytic uremic syndrome (HUS) and HIV infection. The organization of glycolipids, including Gb3, into lipid rafts is central to both pathologies. The fatty acid heterogeneity within the Gb3 lipid moiety plays a central role in assembly within such ordered domains. Differential binding of verotoxins and gp120 to such Gb3 isoforms in model and cell membranes indicates a significant role in the eventual pathogenic outcome. HUS may provide the first example whereby membrane Gb3 organization provides a predictor for tissue selective in vivo pathology.