C-terminal fragments of alpha- and beta-tubulin form amyloid fibrils in vitro and associate with amyloid deposits of familiar cerebral amyloid angiopathy, British type
C-terminal fragments of alpha- and beta-tubulin form amyloid fibrils in vitro and associate with amyloid deposits of familiar cerebral amyloid angiopathy, British type
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DOI：
10.1006/bbrc.1996.0211
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发表时间：
1996-02-06
影响因子：
3.1
通讯作者：
Ghiso, J
中科院分区：
文献类型：
--
作者：
Baumann, MH;Wisniewski, T;Ghiso, J
家族性淀粉样变性，英国型，是一种常染色体显性遗传疾病，以进行性痴呆、痉挛性瘫痪和共济失调为特征。积累的淀粉样蛋白的身份是未知的，因此阻止了疾病的明确分类。生化方法被用来表征淀粉样蛋白沉积物的性质，淀粉样蛋白沉积物形成一个人的脑组织谁死于这种疾病。纯化的组织材料进行胰蛋白酶消化和随后的N-末端序列分析。主要的胰蛋白酶片段产生序列VGINYQPPTVVPGGDLAK。FDLMYAK、GLTVPEL和GYLTVAAVER，它们都是人微管蛋白亚基α和β的C-末端的胰蛋白酶消化片段。基于这些片段序列的合成肽在体外形成淀粉样纤维，符合淀粉样蛋白的特征定义。这些发现表明，α-和β-微管蛋白的C-末端片段与家族性淀粉样变性（英国型）的淀粉样沉积密切相关。(C)出版社：Academic Press Inc.
Familial amyloidosis, British type, is an autosomal dominant disease characterized by progressive dementia, spastic paralysis and ataxia. The identity of the accumulating amyloid is not known, thus preventing the definitive classification of the disease. Biochemical methods were used to characterize the nature of the amyloid deposits form the brain tissue of one individual who died with this disease. The purified tissue material was subjected to trypsin digestion and subsequent N-terminal sequence analysis. Major tryptic fragments yielded the sequences VGINYQPPTVVPGGDLAK. FDLMYAK, GLTVPEL and GYLTVAAVER, which are all tryptic fragments of the C-termini of human tubulin subunits alpha and beta. Synthetic peptides based on the sequences of these fragments formed amyloid fibrils in vitro, fitting the characteristic definition of amyloid. These findings suggest that the C-terminal fragments of both, alpha- and beta-tubulin are closely associated to the amyloid deposits of familial amyloidosis, British type. (C) 1996 Academic Press Inc.