Genetic influence on the structural variations of the abnormal prion protein
Genetic influence on the structural variations of the abnormal prion protein
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DOI：
10.1073/pnas.97.18.10168
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发表时间：
2000-08-29
影响因子：
11.1
通讯作者：
Chen, SG
中科院分区：
文献类型：
--
作者：
Parchi, P;Zou, WQ;Chen, SG
朊病毒疾病的特征是存在异常的朊病毒蛋白PrPSc，这被认为是由在正常PrP异构体中占主导地位的α -螺旋结构转化为抵抗蛋白酶K （PK）的β -片结构产生的。在人类朊病毒疾病中，根据抗pk核心片段电泳迁移的差异，可以区分两种主要类型的PrPSc， 1型和2型。本研究利用蛋白测序技术鉴定了36例朊病毒疾病中PrPSc的PK切割位点。我们发现1型和2型PrPSc分别在残基82和残基97处有两个主要的裂解位点，并且沿残基74-102分布有许多次级裂解位点。因此，我们确定了PrPSc中的三个区域：一个n端（残基23-73）始终对PK敏感，一个c端（残基103-231）始终对PK抗性，第三个可变区域（残基74-102），其中PK切割的位置可能反映了β -片结构的程度，主要随密码子129上PrP基因型的功能而变化。
Prion diseases are characterized by the presence of the abnormal prion protein PrPSc, which is believed to be generated by the conversion of the alpha-helical structure that predominates in the normal PrP isoform into a beta-sheet structure resistant to proteinase K (PK). In human prion diseases, two major types of PrPSc, type 1 and 2, can be distinguished based on the difference in electrophoretic migration of the PK-resistant core fragment. In this study, protein sequencing was used to identify the PK cleavage sites of PrPSc in 36 cases of prion diseases. We demonstrated two primary cleavage sites at residue 82 and residue 97 for type 1 and type 2 PrPSc, respectively, and numerous secondary cleavages distributed along the region spanning residues 74-102. Accordingly, we identify three regions in PrPSc: one N-terminal (residues 23-73) that is invariably PK-sensitive, one C-terminal (residues 103-231) that is invariably PK-resistant, and a third variable region (residues 74-102) where the site of the PK cleavage, likely reflecting the extent of the beta-sheet structure, varies mostly as a function of the PrP genotype at codon 129.