Heegaard N H, Heegaard P M, Roepstorff P, Robey F A
Department of Autoimmunology, Statens Serum Institut, Copenhagen, Denmark.
Eur J Biochem. 1996 Aug 1;239(3):850-6. doi: 10.1111/j.1432-1033.1996.0850u.x.
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.
淀粉样蛋白P成分（AP）是一种天然存在的糖蛋白，存在于血清和基底膜中。AP也是所有类型淀粉样蛋白的组成成分，包括在患有阿尔茨海默病和唐氏综合征的个体中发现的淀粉样蛋白。由于已发现AP能与作为淀粉样沉积物成分的某些糖胺聚糖强烈且特异性地结合，因此AP可能在淀粉样蛋白的维持中起重要作用。在本研究中，我们分离并鉴定了AP的两个蛋白水解片段，它们负责其肝素结合活性。这两个片段均与已发表的肝素结合序列不符。通过使用合成肽的固相抑制试验研究了这些肽（AP的氨基酸残基27 - 38和192 - 203）活性的结构要求。AP -（192 - 203）肽以25μM的IC50抑制AP与肝素的Ca（2 +）依赖性结合，而AP -（27 - 38）肽和AP -（33 - 38）肽的IC50分别为10μM和2μM。了解活性AP肽的结构和功能将有助于开发针对淀粉样蛋白的诊断和治疗方法。
