Structure of the recombinant full-length hamster prion protein PrP(29-231): The N terminus is highly flexible
Structure of the recombinant full-length hamster prion protein PrP(29-231): The N terminus is highly flexible
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DOI：
10.1073/pnas.94.25.13452
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发表时间：
1997-12-09
影响因子：
11.1
通讯作者：
Dyson, HJ
中科院分区：
文献类型：
--
作者：
Donne, DG;Viles, JH;Dyson, HJ
Prion病似乎是由PrP的构象变化引起的，PrP从良性的细胞形式PrPC转变为传染性的PrPSc；因此，关于PrP结构的详细信息可能为这些疾病的发展机制提供重要的见解。本研究用多维核磁共振技术研究了重组叙利亚仓鼠PrP残基29-231[PrP(29-231)]的二级结构。化学位移指数分析和核Overhaser效应数据表明，PrP(29-231)含有三个螺旋和可能的一个短链，最引人注目的是全长PrP中30-124个残基的化学位移的随机卷曲性质。虽然PrP(121-231)的二级结构元素与小鼠PrP(121-231)相似，但PrP(29-231)的二级结构边界与小鼠PrP(121-231)不同，与叙利亚仓鼠PrP(90-231)的二级结构边界相似。共振指定或PrP(29-231)和PrP(90-231)的比较表明，额外的残基与结构核心之间可能存在瞬时相互作用。利用异核[H-1]-N-15核Overhauser效应进行的骨架动力学研究表明，几乎一半的PrP(29-231)残基29-124是高度柔性的。这个塑性区域可以通过模板辅助形成β-结构来将PrPC转化为PrPSc。
The prion diseases seem to be caused by a conformational change of the prion protein (PrP) from the benign cellular form PrPC to the infectious scrapie form PrPSc; thus, detailed information about PrP structure may provide essential insights into the mechanism by which these diseases develop. In this study, the secondary structure of the recombinant Syrian hamster PrP of residues 29-231 [PrP(29-231)] is investigated by multidimensional heteronuclear NMR. Chemical shift index analysis and nuclear Overhauser effect data show that PrP(29-231) contains three helices and possibly one short beta-strand, Most striking is the random-coil nature of chemical shifts for residues 30-124 in the full-length PrP. Although the secondary structure elements are similar to those found in mouse PrP fragment PrP(121-231), the secondary structure boundaries of PrP(29-231) are different from those in mouse PrP(121-231) but similar to those found in the structure of Syrian hamster PrP(90-231). Comparison of resonance assignments or PrP(29-231) and PrP(90-231) indicates that there may be transient interactions between the additional residues and the structured core. Backbone dynamics studies done by using the heteronuclear [H-1]-N-15 nuclear Overhauser effect indicate that almost half of PrP(29-231), residues 29-124, is highly flexible. This plastic region could feature in the conversion of PrPC to PrPSc by template-assisted formation of beta-structure.