Department of Bionanotechnology, Gachon University, Gyeonggi, Korea.
Exp Mol Med. 2013 Aug 2;45(8):e34. doi: 10.1038/emm.2013.63.
Cellular prion protein, a membrane protein, is expressed in all mammals. Prion protein is also found in human blood as an anchorless protein, and this protein form is one of the many potential sources of misfolded prion protein replication during transmission. Many studies have suggested that β-amyloid1-42 oligomer causes neurotoxicity associated with Alzheimer's disease, which is mediated by the prion protein that acts as a receptor and regulates the hippocampal potentiation. The prevention of the binding of these proteins has been proposed as a possible preventative treatment for Alzheimer's disease; therefore, a greater understanding of the binding hot-spots between the two molecules is necessary. In this study, the epitope mapping immunoassay was employed to characterize binding epitopes within the prion protein and complementary epitopes in β-amyloid. Residues 23-39 and 93-119 in the prion protein were involved in binding to β-amyloid1-40 and 1-42, and monomers of this protein interacted with prion protein residues 93-113 and 123-166. Furthermore, β-amyloid antibodies against the C-terminus detected bound β-amyloid1-42 at residues 23-40, 104-122 and 159-175. β-Amyloid epitopes necessary for the interaction with prion protein were not determined. In conclusion, charged clusters and hydrophobic regions of the prion protein were involved in binding to β-amyloid1-40 and 1-42. The 3D structure appears to be necessary for β-amyloid to interact with prion protein. In the future, these binding sites may be utilized for 3D structure modeling, as well as for the pharmaceutical intervention of Alzheimer's disease.
细胞朊蛋白是一种膜蛋白，在所有哺乳动物中表达。朊蛋白也作为一种无锚定蛋白存在于人类血液中，这种蛋白质形式是在传播过程中错误折叠朊蛋白复制的许多潜在来源之一。许多研究表明，β-淀粉样蛋白 1-42 寡聚体引起与阿尔茨海默病相关的神经毒性，其由作为受体的朊蛋白介导，并调节海马增强作用。已经提出了防止这些蛋白质结合作为阿尔茨海默病可能的预防治疗方法；因此，需要更好地了解两种分子之间的结合热点。在这项研究中，采用表位作图免疫测定法来表征朊蛋白内的结合表位和β-淀粉样蛋白中的互补表位。朊蛋白中的残基 23-39 和 93-119 参与与β-淀粉样蛋白 1-40 和 1-42 的结合，该蛋白质的单体与朊蛋白残基 93-113 和 123-166 相互作用。此外，针对 C 末端的β-淀粉样蛋白抗体检测到在残基 23-40、104-122 和 159-175 处结合的β-淀粉样蛋白 1-42。尚未确定与朊蛋白相互作用所需的β-淀粉样蛋白表位。总之，朊蛋白的带电簇和疏水区参与与β-淀粉样蛋白 1-40 和 1-42 的结合。3D 结构似乎是β-淀粉样蛋白与朊蛋白相互作用所必需的。将来，这些结合位点可能用于 3D 结构建模，以及阿尔茨海默病的药物干预。
