MAPPING THE SURFACE RESIDUES ON MURINE HDL-ASSOCIATED SERUM AMYLOID A REVEALS SIGNIFICANT DIFFERENCES BETWEEN THE TWO MAJOR ISOFORMS

摘要

During an acute-phase response mammalian species produce two very similar isoforms of serum amyloid A (SAA) associated with high density lipoprotein (HDL) (1). In mice only the 1.1 isoform is amyloidogenic, eventhough SAA1.1 and SAA2.1 have 91% sequence identity (2). We attempted to determine if differences in conformation existed between these two isoforms and whether this contributed to their difference in amyloidogenic potential. Applying conventional methods (crystallography, NMR) to examine SAA's 3-dimentional structure is complicated by its hydrophobic nature. To circumvent this problem we used three different chemical modifiers to explore the solvent exposed residues of native SAA associated with HDL. We investigated tryptophan (W), tyrosine (Y) and lysine