PRION PROTEIN-PEPTIDES INDUCE ALPHA-HELIX TO BETA-SHEET CONFORMATIONAL TRANSITIONS
PRION PROTEIN-PEPTIDES INDUCE ALPHA-HELIX TO BETA-SHEET CONFORMATIONAL TRANSITIONS
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DOI：
10.1021/bi00013a006
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发表时间：
1995-04-04
期刊：
影响因子：
2.9
通讯作者：
PRUSINER, SB
中科院分区：
文献类型：
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作者：
NGUYEN, J;BALDWIN, MA;PRUSINER, SB
合成肽的结构对应于推定的二级结构在细胞朊病毒蛋白PrPC的区域进行了研究，作为模型的构象转变的特点，在形成的致病性亚型，PrPSc。转基因研究认为，这些PrP同种型在PrPSc的形成过程中相互作用，这涉及PrPC的一个或多个螺旋的解折叠，然后再折叠成β-折叠。PrP残基109-122（Hi），预测为α-螺旋，在水性缓冲液中形成β-折叠，而较长的肽104-122（104 H1）和肽129-141（H2）在溶液中具有卷曲或α-螺旋结构。104 H1和H2在与H1相互作用后均转化为β-折叠，如通过傅立叶变换红外（FTIR）和圆二色性（CD）光谱所监测的。这种转化是序列特异性的，因为小鼠（Mo）H1与叙利亚仓鼠（SHa）在两个残基上不同，在将SHa 104 H1转化为β折叠形式方面效率低下。在含有10%乙腈的缓冲液中，通过加入低至1%的H1，104 H1被转化为β-折叠形式。此外，与H1具有相似物理性质的AP 11-25和A β 25-35肽不能将H2转化为β折叠形式。这些研究如何近似朊病毒复制的基础PrP的结构转变仍有待确定。
The structures of synthetic peptides corresponding to regions of putative secondary structure in the cellular prion protein PrPC were studied as models for the conformational transition that features in the formation of the pathogenic isoform, PrPSc. Transgenetic studies argue that these PrP isoforms interact during the formation of PrPSc, which involves the unfolding of one or more helices of PrPC followed by refolding into beta-sheets, PrP residues 109-122 (Hi), which were predicted to be alpha-helical, form beta-sheets in aqueous buffers, while the longer peptide 104-122 (104H1) and also peptide 129-141 (H2) have coil or alpha-helical structures in solution. Both 104H1 and H2 were converted into beta-sheets upon interaction with H1, as monitored by Fourier transform infrared (FTIR) and circular dichroism (CD) spectroscopy. The conversion was sequence-specific since mouse (Mo)H1, which differs from Syrian hamster (SHa) at two residues, was inefficient at converting SHa104H1 into the beta-sheet form. In buffers containing 10% acetonitrile, 104H1 was converted into the beta-sheet form by addition of as little as 1% H1. In addition, AP 11-25 and A beta 25-35 peptides with similar physical properties to H1 were incapable of converting H2 into the beta-sheet form. How well these studies approximate the structural transitions in PrP that underlie the replication of prions remains to be established.