LIGAND-BINDING SITES IN HUMAN SERUM AMYLOID-P COMPONENT

Amyloid P component (AP) is a naturally occurring glycoprotein that is found in serum and basement membranes, AP is also a component of all types of amyloid, including that found in individuals who suffer from Alzheimer's disease and Down's syndrome. Because AP has been found to bind strongly and specifically to certain glycosaminoglycans that are components of amyloid deposits, AP may play an important role in the m aintenance of amyloid. In the present work, we isolated and identified two proteolytic fragments of AP that are responsible for its heparin- binding activity. Neither fragment corresponds to published heparin-bi nding sequences. The structural requirements for activity of the pepti des (amino acid residues 27-38 and 192-203 of AP) were examined by mea ns of solid-phase inhibition assays with synthetic peptides, AP-(192-2 03)-peptide inhibits the Ca2+-dependent binding of AP to heparin with an IC50 of 25 mu M, while the IC50 of AP-(27-38)-peptide and AP-(33-38 )-peptide are 10 mu M and 2 mu M, respectively, The understanding of t he structure and function of active AP peptides will be useful for dev elopment of amyloid-targeted diagnostics and therapeutics.