Alzheimer disease tangles share immunological similarities with multiphosphorylation repeats in the two large neurofilament proteins.
Alzheimer disease tangles share immunological similarities with multiphosphorylation repeats in the two large neurofilament proteins.
复制标题
阿尔茨海默病缠结与两种大神经丝蛋白中的多磷酸化重复具有免疫学相似性。
DOI：
10.1073/pnas.85.19.7384
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发表时间：
1988
影响因子：
11.1
通讯作者：
Trojanowski,JQ
中科院分区：
文献类型：
--
作者：
Lee,VM;OtvosJr,L;Schmidt,ML;Trojanowski,JQ
免疫学和结构分析的神经丝（NF）蛋白与超过500个抗NF单克隆抗体（mAb）列举的表位共享的NF蛋白和阿尔茨海默氏症神经元缠结。我们确定了大鼠最重NF亚基的多磷酸化结构域-Lys-Ser-Pro-Xaa串联重复序列（其中Xaa是一个小的不带电荷的氨基酸，丝氨酸被磷酸化）-作为检测神经元缠结的500多个mAb中16个mAb中15个的决定因素。这16种单克隆抗体中的大多数（11种）也识别先前表征的人中等大小NF亚基中的多磷酸化重复。然而，虽然这些单克隆抗体共享识别NFT的能力，这16个单克隆抗体的抗原结合结构域代表13个独立的类，基于它们对来自大鼠最重NF亚基和人中等大小NF亚基多磷酸化位点的12个合成肽、10个不同物种的NF亚基和正常人tau蛋白的差异识别。我们的结论是，NFTs共享高度特异性的免疫和结构特性与特定的大鼠最重的NF亚基和人类中等大小的NF亚基多磷酸化重复。
Immunological and structural analyses of neurofilament (NF) proteins with greater than 500 anti-NF monoclonal antibodies (mAbs) enumerated epitopes shared by NF proteins and Alzheimer neurofibrillary tangles. We identified the multiphosphorylation domain of the rat heaviest NF subunit--tandem repeats of Lys-Ser-Pro-Xaa (where Xaa is a small uncharged amino acid and serine is phosphorylated)--as the determinant recognized by 15 of the 16 mAbs from this collection of greater than 500 mAbs that detected neurofibrillary tangles. Most (11) of these 16 mAbs also recognized the previously characterized multiphosphorylation repeat in the human middle sized NF subunit. However, although these mAbs shared the ability to recognize NFTs, the antigen-binding domains of these 16 mAbs represented 13 separate classes based on their differential recognition of 12 synthetic peptides derived from the rat heaviest NF subunit and the human middle-sized NF subunit multiphosphorylation sites, NF subunits of 10 diverse species, and normal human tau protein. We conclude that NFTs share highly specific immunological and structural properties with specific rat heaviest NF subunit and human middle-sized NF subunit multiphosphorylation repeats.