Locally disordered conformer of the hamster prion protein: a crucial intermediate to PrPSc?
Locally disordered conformer of the hamster prion protein: a crucial intermediate to PrPSc?
复制标题
DOI：
10.1021/bi026129y
复制
发表时间：
2002-09
期刊：
影响因子：
2.9
通讯作者：
K. Kuwata;Hua Li;H. Yamada;G. Legname;S. Prusiner;K. Akasaka;T. James
中科院分区：
文献类型：
--
作者：
K. Kuwata;Hua Li;H. Yamada;G. Legname;S. Prusiner;K. Akasaka;T. James
正常细胞同种型朊病毒蛋白 (PrP(C)) 转化为感染性朊病毒蛋白 (PrP(Sc)) 的关键步骤被认为需要一个先前未表征的中间构象异构体 PrP*，它在转化过程中与模板 PrP(Sc) 分子相互作用。通过对叙利亚仓鼠朊病毒蛋白rPrP(90-231)进行变压下的(15)N-(1)H二维NMR测量，我们发现PrP(C)的亚稳态构象异构体在pH 5.2和30℃下以大约1%的群体共存，其中螺旋B和C优先无序。虽然身份尚未得到证实，但这种观察到的亚稳态构象异构体在逻辑上最符合 PrP* 或密切相关的前体。这种亚稳态构象异构体的结构特征与朊病毒蛋白的现有免疫学和病理学信息一致。
A crucial step for transformation of the normal cellular isoform of the prion protein (PrP(C)) to the infectious prion protein (PrP(Sc)) is thought to entail a previously uncharacterized intermediate conformer, PrP*, which interacts with a template PrP(Sc) molecule in the conversion process. By carrying out (15)N-(1)H two-dimensional NMR measurements under variable pressure on Syrian hamster prion protein rPrP(90-231), we found a metastable conformer of PrP(C) coexisting at a population of approximately 1% at pH 5.2 and 30 degrees C, in which helices B and C are preferentially disordered. While the identity is still unproven, this observed metastable conformer is most logically PrP* or a closely related precursor. The structural characteristics of this metastable conformer are consistent with available immunological and pathological information about the prion protein.