Prion rods contain an inert polysaccharide scaffold
Prion rods contain an inert polysaccharide scaffold
复制标题
DOI：
10.1515/bc.1999.165
复制
发表时间：
1999-11-01
影响因子：
3.7
通讯作者：
Riesner, D
中科院分区：
文献类型：
--
作者：
Appel, TR;Dumpitak, C;Riesner, D
发现了一种主要由1，4-连接的葡萄糖单元组成的多糖与朊病毒棒相关，朊病毒棒主要由N-末端截短的朊病毒蛋白（PrP 27-30）的不溶性聚集体组成，表现出淀粉样蛋白的超微结构和着色特性。该多糖在组成上不同于Asn连接的寡糖和朊病毒蛋白的GPI锚。使用两种不同的纯化方案从羊瘙痒病感染的仓鼠脑中制备朊病毒棒。用蛋白酶K长时间消化棒可使PrP减少至少500倍，留下约10%（w/w）的样品作为不溶性残余物。通过酸水解残余物仅获得葡萄糖，甲基化分析显示80%的1，4-、15%的1，6-和5%的1，4，6-连接的葡萄糖单元。物理和化学性质以及末端葡萄糖单元的不存在表明多糖的分子量非常高。没有证据表明PrP和多糖之间存在共价键。这种多糖确实有助于朊病毒棒不同寻常的化学和物理稳定性，就像支架一样。一个潜在的结构和/或功能的相关性的多糖支架进行了讨论。
A polysaccharide consisting of mainly 1,4-linked glucose units was found associated with prion rods, which are composed mainly of insoluble aggregates of the N-terminally truncated prion protein (PrP 27-30) exhibiting the ultrastructural and tinctorial properties of amyloid. The polysaccharide differs in composition from the Asn-linked oligosaccharides and the GPI-anchor of the prion protein. Prion rods were prepared from scrapie-infected hamster brains using two different purification protocols. Prolonged digestion of rods with proteinase K reduced PrP by a factor of at least 500, leaving about 10% (w/w) of the sample as an insoluble remnant. Only glucose was obtained by acid hydrolysis of the remnant and methylation analysis showed 80% 1,4-, 15% 1,6- and 5% 1,4,6-linked glucose units. The physical and chemical properties as well as the absence of terminal glucose units indicate a very high molecular mass of the polysaccharide. No evidence was found for covalent bonds between PrP and the polysaccharide. The polysaccharide certainly contributes to the unusual chemical and physical stability of prion rods, acting like a scaffold. A potential structural and/or functional relevance of the polysaccharide scaffold is discussed.