Reversible conversion of monomeric human prion protein between native and fibrilogenic conformations
Reversible conversion of monomeric human prion protein between native and fibrilogenic conformations
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DOI：
10.1126/science.283.5409.1935
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发表时间：
1999-03-19
期刊：
影响因子：
56.9
通讯作者：
Collinge, J
中科院分区：
文献类型：
--
作者：
Jackson, GS;Hosszu, LLP;Collinge, J
Prion的传播涉及到将细胞内的Prion蛋白(PrPc)转化为疾病特异性的异构体PrPSc，从主要的α-螺旋结构转变为β-折叠结构。在这里，建立了重组人PrP可以在天然a构象和致密、高度溶解、富含β结构的单体形式之间切换的条件。可溶性β形式(β-PrP)表现出对蛋白酶kappa消化的部分抵抗力，这是PrPSc的特征，是纤维结构的直接前体，与从疾病脑中分离的纤维结构非常相似。PrPc在合适的细胞间隔内转化为β-PrP，并随后通过分子间结合稳定它，为Pron的繁殖提供了分子机制。
Prion propagation involves the conversion of cellular prion protein (PrPc) into a disease-specific isomer, PrPSc, shifting from a predominantly alpha-helical to beta-sheet structure. Here, conditions were established in which recombinant human PrP could switch between the native a conformation, characteristic of PrPc, and a compact, highly soluble, monomeric form rich in beta structure. The soluble beta form (beta-PrP) exhibited partial resistance to proteinase kappa digestion, characteristic of PrPSc, and was a direct precursor of fibrillar structures closely similar to those isolated from diseased brains. The conversion of PrPc to beta-PrP in suitable cellular compartments, and its subsequent stabilization by intermolecular association, provide a molecular mechanism for prion propagation.