Atomic structures suggest determinants of transmission barriers in mammalian prion disease.
Atomic structures suggest determinants of transmission barriers in mammalian prion disease.
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DOI：
10.1021/bi101803k
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发表时间：
2011-04-05
期刊：
影响因子：
2.9
通讯作者：
Eisenberg D
中科院分区：
文献类型：
--
作者：
Apostol MI;Wiltzius JJ;Sawaya MR;Cascio D;Eisenberg D
朊病毒是一类独特的无核酸病原体。由它在一个物种的成员之间传播的致命疾病，在某些情况下传播给其他物种的成员，引起了公共卫生问题。传播性和物种间传播的障碍被认为是由一个物种个体的病理蛋白质构象在另一个物种中产生病理构象的程度引起的。然而，这一假设从未在原子水平上得到说明。在这里，我们展示了来自人类、小鼠和仓鼠PrP的同一片段的三个x射线原子结构，这对于形成淀粉样蛋白至关重要，并在PrP播种实验中赋予物种特异性。这些结构揭示了不同的序列编码不同的立体拉链，并表明这些拉链结构的不同程度导致了朊病毒疾病的传播障碍，例如保护人类免受牛海绵状脑病（BSE）和慢性消耗性疾病（CWD）的传播障碍。
Prion represents a unique class of pathogens devoid of nucleic acid. The deadly diseases transmitted by it between members of one species and, in certain instances to members of other species, present a public health concern. Transmissibility and the barriers to transmission between species have been suggested to arise from the degree to which a pathological protein conformation from an individual of one species can seed a pathological conformation in another species. However, this hypothesis has never been illustrated at an atomic level. Here we present three X-ray atomic structures of the same segment from human, mouse, and hamster PrP, which is critical for forming amyloid and confers species specificity in PrP seeding experiments. The structures reveal that different sequences encode different steric zippers and suggest that the degree of dissimilarity of these zipper structures gives rise to transmission barriers in prion disease, such as those that protect humans from acquiring bovine spongiform encephalopathy (BSE) and chronic wasting disease (CWD).
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DOI：
10.1073/pnas.0409008102
发表时间：
2005-01-18
影响因子：
11.1
作者：
Gossert, AD;Bonjour, S;Wüthrich, K
通讯作者：
Wüthrich, K
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
5.4
作者：
Browning, SR;Mason, GL;Telling, GC
通讯作者：
Telling, GC
影响因子：
64.8
作者：
GRIFFITH, JS
通讯作者：
GRIFFITH, JS
影响因子：
2.2
作者：
KIRKWOOD, JK;CUNNINGHAM, AA
通讯作者：
CUNNINGHAM, AA