NR AHSI
AU Mahfoud,R.; Garmy,N.; Maresca,M.; Yahi,N.; Puigserver,A.; Fantini,J.
TI Identification of a common sphingolipid-binding domain in Alzheimer, prion, and HIV-1 proteins
QU The Journal of Biological Chemistry 2002 Mar 29; 277(13): 11292-6
PT journal article
AB The V3 loop of the human immunodeficiency virus (HIV)-1 surface envelope glycoprotein gp120 is a sphingolipid-binding domain mediating the attachment of HIV-1 to plasma membrane microdomains (rafts). Sphingolipid-induced conformational changes in gp120 are required for HIV-1 fusion. Galactosylceramide and sphingomyelin have been detected in highly purified preparations of prion rods, suggesting that the prion protein (PrP) may interact with selected sphingolipids. Moreover, a major conformational transition of the Alzheimer beta-amyloid peptide has been observed upon interaction with sphingolipid-containing membranes. Structure similarity searches with the combinatorial extension method revealed the presence of a V3-like domain in the human prion protein PrP and in the Alzheimer beta-amyloid peptide. In each case, synthetic peptides derived from the predicted V3-like domain were found to interact with monomolecular films of galactosylceramide and sphingomyelin at the air-water interface. The V3-like domain of PrP is a disulfide-linked loop (Cys(179)-Cys(214)) that includes the E200K mutation site associated with familial Creutzfeldt-Jakob disease. This mutation abrogated sphingomyelin recognition. The identification of a common sphingolipid-binding motif in gp120, PrP, and beta-amyloid peptide underscores the role of lipid rafts in the pathogenesis of HIV-1, Alzheimer, and prion diseases and may provide new therapeutic strategies.
MH Alzheimer Disease/*metabolism; Amino Acid Sequence; HIV-1/*metabolism; Models, Molecular; Molecular Sequence Data; Mutation; Prions/*metabolism; Protein Binding; Sphingolipids/*metabolism; Viral Proteins/*metabolism
AD Institut Mediterraneen de Recherche en Nutrition, Unite Mixte de Recherche-Institut National de la recherche Agronomique 1111, Faculte des Sciences St-Jerome, 13397 Marseille Cedex 20, France.
SP englisch
PO USA