Glycoform-selective prion formation in sporadic and familial forms of prion disease.
Glycoform-selective prion formation in sporadic and familial forms of prion disease.
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DOI：
10.1371/journal.pone.0058786
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Zou WQ
中科院分区：
文献类型：
--
作者：
Xiao X;Yuan J;Haïk S;Cali I;Zhan Y;Moudjou M;Li B;Laplanche JL;Laude H;Langeveld J;Gambetti P;Kitamoto T;Kong Q;Brandel JP;Cobb BA;Petersen RB;Zou WQ
在大多数散发性朊病毒疾病的情况下，在两个N-连接的糖基化位点处糖基化的细胞朊病毒蛋白（PrPC）的四种糖型转化为它们的病理形式（PrPSc）。然而，在最近鉴定的朊蛋白酶敏感性朊病毒病（VPSPr）中，PrPSc的一个突出分子特征是不存在二糖基化形式，这在家族性克雅氏病（fCJD）中也是显著的，其与PrP在残基180处从瓦尔突变为Ile（fCJDV 180 I）或在残基183处从Thr突变为Ala（fCJDT 183 A）有关。在这里，我们报告说，fCJDV 180 I，而不是fCJDT 183 A，表现出蛋白酶K（PK）-耐PrP（PrPres），这是显着相似的VPSPr中观察到的，表现出五步梯状电泳轮廓，VPSPr的分子标志。值得注意的是，在fCJDV 180 I和VPSPr中不存在二糖基化的PrPres种类同样可归因于在残基181的第一个N-连接的糖基化位点处不存在糖基化的PrPres，如在fCJDT 183 A中。与fCJDT 183 A相反，VPSPr和fCJDV 180 I在PK处理前均在二糖基化和单糖基化（mono 181）PrP上的残基181处显示糖基化。此外，来自培养细胞的具有典型糖型特征的PrPV 180 I在PK处理后产生可检测的PrPres，其除了单糖基化和非糖基化形式之外还含有二糖基化PrP。综上所述，我们目前的体内和体外研究表明，散发性VPSPr和家族性CJDV 180 I共享一个独特的糖型选择性朊病毒形成途径，其中二糖基化和单181 PrPC转化为PrPSc受到抑制，可能是由显性负效应或其他辅助因子。
The four glycoforms of the cellular prion protein (PrPC) variably glycosylated at the two N-linked glycosylation sites are converted into their pathological forms (PrPSc) in most cases of sporadic prion diseases. However, a prominent molecular characteristic of PrPSc in the recently identified variably protease-sensitive prionopathy (VPSPr) is the absence of a diglycosylated form, also notable in familial Creutzfeldt-Jakob disease (fCJD), which is linked to mutations in PrP either from Val to Ile at residue 180 (fCJDV180I) or from Thr to Ala at residue 183 (fCJDT183A). Here we report that fCJDV180I, but not fCJDT183A, exhibits a proteinase K (PK)-resistant PrP (PrPres) that is markedly similar to that observed in VPSPr, which exhibits a five-step ladder-like electrophoretic profile, a molecular hallmark of VPSPr. Remarkably, the absence of the diglycosylated PrPres species in both fCJDV180I and VPSPr is likewise attributable to the absence of PrPres glycosylated at the first N-linked glycosylation site at residue 181, as in fCJDT183A. In contrast to fCJDT183A, both VPSPr and fCJDV180I exhibit glycosylation at residue 181 on di- and monoglycosylated (mono181) PrP prior to PK-treatment. Furthermore, PrPV180I with a typical glycoform profile from cultured cells generates detectable PrPres that also contains the diglycosylated PrP in addition to mono- and unglycosylated forms upon PK-treatment. Taken together, our current in vivo and in vitro studies indicate that sporadic VPSPr and familial CJDV180I share a unique glycoform-selective prion formation pathway in which the conversion of diglycosylated and mono181 PrPC to PrPSc is inhibited, probably by a dominant-negative effect, or by other co-factors.
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影响因子：
34.7
作者：
Frost, Bess;Diamond, Marc I.
通讯作者：
Diamond, Marc I.
影响因子：
2.9
作者：
Nishina, Koren A.;Deleault, Nathan R.;Supattapone, Surachai
通讯作者：
Supattapone, Surachai
影响因子：
11
作者：
Giaccone, G.;Di Fede, G.;Tagliavini, F.
通讯作者：
Tagliavini, F.
影响因子：
5.4
作者：
KASCSAK, RJ;RUBENSTEIN, R;DIRINGER, H
通讯作者：
DIRINGER, H
影响因子：
5.4
作者：
PRIOLA, SA;CAUGHEY, B;CHESEBRO, B
通讯作者：
CHESEBRO, B