V180I mutation of the prion protein gene associated with atypical PrPSc glycosylation
V180I mutation of the prion protein gene associated with atypical PrPSc glycosylation
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DOI：
10.1016/j.neulet.2006.08.008
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发表时间：
2006-11-20
影响因子：
2.5
通讯作者：
Peoc'h, Katell
中科院分区：
文献类型：
--
作者：
Chasseigneaux, Stephanie;Haik, Stephane;Peoc'h, Katell
在1例法国克雅氏病(CJD)患者中发现180位氨基酸残基突变为异亮氨酸。该突变位于细胞蛋白(PrPc)的两个N-糖基化位点之一的附近。Western印迹分析显示，致病蛋白K抗性PrP(PrPSc)亚型在脑内积聚，但明显缺乏二糖基条带。在CHO细胞中表达的突变蛋白被正确地糖基化，这表明PrPSc的非典型糖基化模式不是由于180位突变所致。这些结果表明，突变PrP1801的二糖基化形式阻止了它向致病突变形式PrPSc1801的转化。支持N-连接的糖链在PrP转化过程中的中心作用。(C)2006爱思唯尔爱尔兰有限公司。保留所有权利。
A valine to isoleucine mutation at residue 180 was identified in a French patient with Creutzfeldt-Jakob disease (CJD). The mutation is located in the close vicinity of one of the two N-glycosylation sites of the cellular prion protein (PrPc). Western blot analysis revealed accumulation in the brain of the pathogenic protemase K-resistant PrP (PrPSc) isoform with the notable absence of the diglycosylated band. The mutant protein expressed in CHO cells was correctly glycosylated, suggesting that the atypical glycosylation pattern of PrPSc was not due to the mutation at position 180. These results suggest that the diglycosylated form of the mutant PrP1801 prevents its conversion into the pathogenic mutant form PrPSc1801. supporting a central role of N-linked glycan chains in the PrP conversion process. (c) 2006 Elsevier Ireland Ltd. All rights reserved.