Thr but Asn of the N-glycosylation sites of PrP is indispensable for its misfolding
Thr but Asn of the N-glycosylation sites of PrP is indispensable for its misfolding
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DOI：
10.1016/j.bbrc.2008.03.014
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发表时间：
2008-05-16
影响因子：
3.1
通讯作者：
Kitamoto, Tetsuyuki
中科院分区：
文献类型：
--
作者：
Ikeda, Shino;Kobayashi, Atsushi;Kitamoto, Tetsuyuki
Prion蛋白(PrP)含有两个N连接的糖基化位点。目前还不清楚哪种氨基酸取代对N-连接糖基化的消除最有效。为了确定N-连接糖基化位点的氨基酸替换对小鼠PrP转换效率的影响，我们测试了所有19个氨基酸替换中的任何一个(密码子180、182、196或198)。诱变的PrP的转化效率高度依赖于新引入的氨基酸本身，而不考虑瘙痒病感染的小鼠神经母细胞瘤细胞中是否存在眨眼糖基化。大多数在眨眼糖基化位点ASN残基发生替换的突变PrP具有转化能力，而大多数在Thr残基发生取代的突变PrP是不具备转化能力的。这些发现强调，N连接的糖基化位点上的ASN残基是可替换的，可以在不直接影响蛋白质功能的情况下取消眨眼糖基化。(C)2008 Elsevier Inc.保留所有权利。
Prion protein (PrP) contains two N-linked glycosylation sites. It is unknown which amino acid substitution contributes most efficiently to the abolishment of N-linked glycosylations. To define the influence of amino acid substitution at the N-linked glycosylation sites on the conversion efficiency of mouse PrP, we tested each of all 19 amino acid substitutions at either one of the Winked glycosylation sites (codon 180, 182, 196 or 198). The conversion efficiency of the mutagenized PrP was highly dependent on the newly introduced amino acid itself regardless of the absence of Winked glycosylation in scrapie-infected mouse neuroblastoma cells. The majority of mutant PrP with substitutions at the Asn residues of the Winked glycosylation sites were conversion-competent, whereas most mutant PrP with substitutions at the Thr residues were conversion-incompetent. These findings emphasize that the Asn residues of the N-linked glycosylation sites are replaceable to abolish Winked glycosylations without directly affecting the protein function. (C) 2008 Elsevier Inc. All rights reserved.