Abeta(1-40) fibril polymorphism implies diverse interaction patterns in amyloid fibrils.-猫眼课题宝

DOI：

10.1016/j.jmb.2008.11.005

发表时间：

2009-02-27

期刊：

Journal of molecular biology

影响因子：

5.6

通讯作者：

中科院分区：

生物学2区

文献类型：

作者：

Meinhardt J;Sachse C;Hortschansky P;Grigorieff N;Fändrich M

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6760659/

淀粉样原纤维表征了包括阿尔茨海默病、克雅氏病和II型糖尿病在内的多种人类疾病。阿尔茨海默氏淀粉样蛋白原纤维由Aβ肽组成，并以一系列结构上不同的原纤维形态出现。使用冷冻电镜和三维重建，我们确定了12个单一的Aβ（1-40）淀粉样纤维的结构特征，所有这些纤维都是在相同的溶液条件下形成的。我们发现，大多数分析的原纤维形成一系列的形态，显示几乎不断改变的结构特性。所观察到的原纤维多态性意味着淀粉样蛋白的形成可以导致，对于相同的多肽序列，许多不同的模式间或残基内的相互作用。这一特性与天然单体蛋白质折叠反应显著不同，对于一个蛋白质序列，天然单体蛋白质折叠反应仅产生一种有序构象和一组残基间相互作用。

Amyloid fibrils characterize a diverse group of human diseases that includes Alzheimer’s disease, Creutzfeldt-Jakob and type II diabetes. Alzheimer’s amyloid fibrils consist of Aβ peptide and occur in a range of structurally different fibril morphologies. Using electron cryo-microscopy and three-dimensional reconstruction, we have determined here the structural characteristics of twelve single Aβ(1–40) amyloid fibrils, all formed under the same solution conditions. We find that the majority of analyzed fibrils form a range of morphologies that show almost continuously altering structural properties. The observed fibril polymorphism implies that amyloid formation can lead, for the same polypeptide sequence, to many different patterns of inter- or intra-residue interactions. This property differs significantly from native, monomeric protein folding reactions that produce, for one protein sequence, only one ordered conformation and only one set of inter-residue interactions.