Directed selection of a conformational antibody domain that prevents mature amyloid fibril formation by stabilizing Aβ protofibrils
Directed selection of a conformational antibody domain that prevents mature amyloid fibril formation by stabilizing Aβ protofibrils
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DOI：
10.1073/pnas.0703793104
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发表时间：
2007-12-04
影响因子：
11.1
通讯作者：
Faendrich, Marcus
中科院分区：
文献类型：
--
作者：
Habicht, Gernot;Haupt, Christian;Faendrich, Marcus
淀粉样纤维的形成是阿尔茨海默病和其他几种淀粉样变性中常见的生化特征。淀粉样蛋白原纤维的统一结构特征是其特定类型的β-折叠构象，其将这些原纤维与正常蛋白质折叠反应的产物区分开。在这里，我们描述的抗体结构域，称为B10，识别淀粉样蛋白特异性和构象定义的表位的生成。通过噬菌体展示从骆驼科动物抗体结构域的重组文库中选择该抗体结构域。表面等离子体共振、免疫印迹和免疫组织化学显示，该抗体结构域将A β淀粉样蛋白原纤维与解聚的A β肽以及特定的A β寡聚体区分开。抗体结构域具有通过稳定A β原纤维来防止成熟淀粉样蛋白原纤维形成的功能活性。这些数据表明B10在淀粉样纤维的检测或其形成的调制中的可能应用。
The formation of amyloid fibrils is a common biochemical characteristic that occurs in Alzheimer's disease and several other amyloidoses. The unifying structural feature of amyloid fibrils is their specific type of beta-sheet conformation that differentiates these fibrils from the products of normal protein folding reactions. Here we describe the generation of an antibody domain, termed B10, that recognizes an amyloid-specific and conformationally defined epitope. This antibody domain was selected by phage-display from a recombinant library of camelid antibody domains. Surface plasmon resonance, immunoblots, and immunohistochemistry show that this antibody domain distinguishes A beta amyloid fibrils from disaggregated A beta peptide as well as from specific A beta oligomers. The antibody domain possesses functional activity in preventing the formation of mature amyloid fibrils by stabilizing A beta protofibrils. These data suggest possible applications of B10 in the detection of amyloid fibrils or in the modulation of their formation.