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 maintenance 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-binding sequences. The structural requirements for activity of the peptides (amino acid residues 27-38 and 192-203 of AP) were examined by means of solid-phase inhibition assays with synthetic peptides. AP-(192-203)-peptide inhibits the Ca(2+)-dependent binding of AP to heparin with an IC50 of 25 microM, while the IC50 of AP-(27-38)-peptide and AP-(33-38)-peptide are 10 microM and 2 microM, respectively. The understanding of the structure and function of active AP peptides will be useful for development of amyloid-targeted diagnostics and therapeutics.
Heegaard
N H
NH
Department of Autoimmunology, Statens Serum Institut, Copenhagen, Denmark.
Heegaard
P M
PM
Roepstorff
P
P
Robey
F A
FA
D000595:Amino Acid Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D001710:Biotin; D004305:Dose-Response Relationship, Drug; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism; D000683:Serum Amyloid P-Component / Q000187:drug effects / Q000378:metabolism*; D014357:Trypsin / Q000494:pharmacology
D008024:Ligands; D010446:Peptide Fragments; D000683:Serum Amyloid P-Component; D001710:Biotin; D006493:Heparin; D014357:Trypsin