Identification of a Common Sphingolipid-binding Domain in Alzheimer, Prion, and HIV-1 Proteins

摘要: The V3 loop of the human immunodeficiency virus (HIV)-1 surface envelope glycoprotein gp120 is a sphingolipid-binding domain mediating attachment HIV-1 to plasma membrane microdomains (rafts). Sphingolipid-induced conformational changes in are required for fusion. Galactosylceramide and sphingomyelin have been detected highly purified preparations prion rods, suggesting that protein (PrP) may interact with selected sphingolipids. Moreover, major transition Alzheimer beta-amyloid peptide has observed upon interaction sphingolipid-containing membranes. Structure similarity searches combinatorial extension method revealed presence V3-like PrP peptide. In each case, synthetic peptides derived from predicted were found monomolecular films galactosylceramide at air-water interface. disulfide-linked (Cys(179)-Cys(214)) includes E200K mutation site associated familial Creutzfeldt-Jakob disease. This abrogated recognition. identification common motif gp120, PrP, underscores role lipid rafts pathogenesis HIV-1, Alzheimer, diseases provide new therapeutic strategies.