Biochemical and physical properties of the prion protein from two strains of the transmissible mink encephalopathy agent
Biochemical and physical properties of the prion protein from two strains of the transmissible mink encephalopathy agent
复制标题
两种传染性水貂脑病病原体的朊病毒蛋白的生化和物理特性
作者：
R. Bessen;R. Marsh
传染性水貂脑病（Transmissible mink encephalopathy，TME）已传播给叙利亚金黄地鼠，并已鉴定出两种具有不同生物学特性的病原体HYPER（HY）和DrowSY（DY）。在痒病（一种TME样疾病）期间，内源性细胞蛋白朊病毒蛋白（PrPC）被修饰（成为PrPSc）并在大脑中积累。PrPSc对蛋白酶具有部分抗性，并被认为是感染因子的重要成分。从感染HY和DY TME剂菌株的仓鼠中纯化和分析PrP，发现PrPTME在N-月桂酰肌氨酸中沉降的性质、对蛋白酶K消化的敏感性和在聚丙烯酰胺凝胶中的迁移存在差异。PrPC和HY PrPTME可以根据它们在洗涤剂中的相对溶解度和蛋白酶敏感性来区分。PrPTME从DY感染的脑组织共享的溶解度特性的PrP从未感染和HY感染的组织。有限的蛋白酶消化的PrPTME显示聚丙烯酰胺凝胶电泳后的菌株特异性迁移模式。长时间的蛋白酶K处理或N-连接的去糖基化的PrPTME没有消除这种差异，但证明了从DY感染的大脑的PrPTME比HY PrPTME更敏感的蛋白酶消化。用针对合成肽的抗体对PrPTME进行抗原作图，发现在含有氨基酸残基89至103的PrPTME氨基末端的区域中免疫反应性存在菌株特异性差异。这些发现表明，PrPTME从两个代理菌株，虽然来自相同的主机，不同的组成，构象，或两者。我们的结论是PrPTME从HY和DY菌株进行不同的翻译后修饰，可以解释从两个来源的PrPTME的生化特性的差异。这些菌株特异性翻译后事件是否直接导致HY和DY菌株的不同生物学特性仍有待确定。
Transmissible mink encephalopathy (TME) has been transmitted to Syrian golden hamsters, and two strains of the causative agent, HYPER (HY) and DROWSY (DY), have been identified that have different biological properties. During scrapie, a TME-like disease, an endogenous cellular protein, the prion protein (PrPC), is modified (to PrPSc) and accumulates in the brain. PrPSc is partially resistant to proteases and is claimed to be an essential component of the infectious agent. Purification and analysis of PrP from hamsters infected with the HY and DY TME agent strains revealed differences in properties of PrPTME sedimentation in N-lauroylsarcosine, sensitivity to digestion with proteinase K, and migration in polyacrylamide gels. PrPC and HY PrPTME can be distinguished on the basis of their relative solubilities in detergent and protease sensitivities. PrPTME from DY-infected brain tissue shared solubility characteristics of PrP from both uninfected and HY-infected tissue. Limited protease digestion of PrPTME revealed strain-specific migration patterns upon polyacrylamide gel electrophoresis. Prolonged proteinase K treatment or N-linked deglycosylation of PrPTME did not eliminate such differences but demonstrated the PrPTME from DY-infected brain was more sensitive to protease digestion than HY PrPTME. Antigenic mapping of PrPTME with antibodies raised against synthetic peptides revealed strain-specific differences in immunoreactivity in a region of the amino-terminal end of PrPTME containing amino acid residues 89 to 103. These findings indicate that PrPTME from the two agent strains, although originating from the same host, differ in composition, conformation, or both. We conclude that PrPTME from the HY and DY strains undergo different posttranslational modifications that could explain differences in the biochemical properties of PrPTME from the two sources. Whether these strain-specific posttranslational events are directly responsible for the distinct biological properties of the HY and DY agent strains remains to be determined.
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DOI：
10.1073/pnas.83.8.2310
发表时间：
1986-04-01
影响因子：
11.1
作者：
MEYER, RK;MCKINLEY, MP;PRUSINER, SB
通讯作者：
PRUSINER, SB
影响因子：
2.9
作者：
PRUSINER, SB;BOLTON, DC;MCKINLEY, MP
通讯作者：
MCKINLEY, MP
DOI：
10.1111/j.1432-1033.1988.tb14246.x
发表时间：
1988-09-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
TURK, E;TEPLOW, DB;PRUSINER, SB
通讯作者：
PRUSINER, SB
影响因子：
56.9
作者：
BOLTON, DC;MCKINLEY, MP;PRUSINER, SB
通讯作者：
PRUSINER, SB
影响因子：
2.9
作者：
STAHL, N;BALDWIN, MA;PRUSINER, SB
通讯作者：
PRUSINER, SB