Wasmer Christian, Lange Adam, Van Melckebeke Hélène, Siemer Ansgar B, Riek Roland, Meier Beat H
Physical Chemistry, ETH Zurich, 8093 Zurich, Switzerland.
Science. 2008 Mar 14;319(5869):1523-6. doi: 10.1126/science.1151839.
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.
蛋白质的朊病毒形式和非朊病毒形式被认为仅在其三维结构上有所不同，因此三维结构对于朊病毒功能至关重要。然而，迄今为止尚未报道可能具有传染性的纤维状状态的原子分辨率结构。我们基于固态核磁共振约束条件，提出了来自丝状真菌Podospora anserina的HET-s蛋白的朊病毒形成结构域（第218至289位氨基酸残基）的淀粉样纤维的结构模型。基于134个分子内和分子间实验距离约束条件，我们发现HET-s(218-289)形成一个左手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梯子。该结构可能对理解传染性淀粉样状态具有广泛的意义。
