Amyloid fibrils of the HET-s(218-289) prion form a β solenoid with a triangular hydrophobic core
Amyloid fibrils of the HET-s(218-289) prion form a β solenoid with a triangular hydrophobic core
复制标题
DOI：
10.1126/science.1151839
复制
发表时间：
2008-03-14
期刊：
影响因子：
56.9
通讯作者：
Meier, Beat H.
中科院分区：
文献类型：
--
作者：
Wasmer, Christian;Lange, Adam;Meier, Beat H.
普恩和非普恩蛋白质被认为只是在其三维结构上不同，因此这对普恩的功能是至关重要的。然而，到目前为止，还没有关于纤维状态的原子分辨结构的报道，这种结构可能具有传染性。我们提出了一个基于固体核磁共振限制的结构模型，该结构模型来自丝状真菌Podospora anserina的HET-S蛋白的Prion形成结构域(第218到289个残基)。在134个分子内和分子间实验距离限制的基础上，我们发现HET-S(218289)形成了一个左手β螺线管，每个分子形成两个螺旋绕组，一个紧密的疏水核心，至少23个氢键，三个盐桥和两个天冬酰胺阶梯。这种结构可能对理解传染性淀粉样蛋白状态具有广泛的意义。
Prion and nonprion forms of proteins are believed to differ solely in their three- dimensional structure, which is therefore of paramount importance for the prion function. However, no atomic-resolution structure of the fibrillar state that is likely infectious has been reported to date. We present a structural model based on solid- state nuclear magnetic resonance restraints for amyloid fibrils from the prion- forming domain ( residues 218 to 289) of the HET- s protein from the filamentous fungus Podospora anserina. On the basis of 134 intra- and intermolecular experimental distance restraints, we find that HET- s( 218 - 289) forms a left- handed beta solenoid, with each molecule forming two helical windings, a compact hydrophobic core, at least 23 hydrogen bonds, three salt bridges, and two asparagine ladders. The structure is likely to have broad implications for understanding the infectious amyloid state.