EXPRESSION AND ANALYSIS OF HEPARIN-BINDING REGIONS OF THE AMYLOID PRECURSOR PROTEIN OF ALZHEIMERS-DISEASE

Deletion mutagenesis studies have suggested that there are two domains within APP which bind heparan sulphate. These domains have been clone d and expressed in the yeast Pichia pastoris. Both recombinant protein s bound to heparin. One domain (APP316-447) was further characterised by binding studies with peptides encompassing this region. Peptides ho mologous to APP316-346 and APP416-447 were found to bind heparin. Circ ular dichroism studies show that APP416-447 shifted towards an alpha-h elical conformation in the presence of heparin. This study suggests th at heparin-binding domains may lie within regions high in alpha-helica l structure. (C) 1997 Federation of European Biochemical Societies.