Pachahara Sanjai Kumar, Nagaraj Ramakrishnan
CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500007, India.
Biochem Biophys Rep. 2015 Apr 25;2:1-13. doi: 10.1016/j.bbrep.2015.04.005. eCollection 2015 Jul.
The Aβ(16-22) sequence KLVFFAE spans the hydrophobic core of the Aβ peptide and plays an important role in its self-assembly. Apart from forming amyloid fibrils, Aβ(16-22) can self-associate into highly ordered nanotubes and ribbon-like structures depending on the composition of solvent used for dissolution. The Aβ(16-22) sequence which has FF at the 19th and 20th positions would be a good model to investigate peptide self-assembly in the context of aromatic interactions. In this study, self-assembly of Aβ(16-22) and its aromatic analogs obtained by replacement of F19, F20 or both by Y or W was examined after dissolution in fluorinated alcohols and their aqueous mixtures in solvent cluster forming conditions. The results indicate that the presence of aromatic residues Y and W and their position in the sequence plays an important role in self-assembly. We observe the formation of amyloid fibrils and other self-assembled structures such as spheres, rings and beads. Our results indicate that 20% HFIP is more favourable for amyloid fibril formation as compared to 20% TFE, when F is replaced with Y or W. The dissolution of peptides in DMSO followed by evaporation of solvent and dissolution in water appears to greatly influence peptide conformation, morphology and cross-β content of self-assembled structures. Our study shows that positioning of aromatic residues F, Y and W have an important role in directing self-assembly of the peptides.
Aβ(16 - 22)序列KLVFFAE跨越Aβ肽的疏水核心，在其自组装过程中发挥重要作用。除了形成淀粉样纤维外，Aβ(16 - 22)还能根据用于溶解的溶剂组成自缔合形成高度有序的纳米管和带状结构。在第19和20位具有FF的Aβ(16 - 22)序列将是研究芳香族相互作用背景下肽自组装的良好模型。在本研究中，在溶剂簇形成条件下将Aβ(16 - 22)及其通过将F19、F20或两者替换为Y或W而获得的芳香族类似物溶解在氟化醇及其水性混合物中后，对其自组装进行了研究。结果表明，芳香族残基Y和W的存在及其在序列中的位置在自组装中起重要作用。我们观察到了淀粉样纤维以及其他自组装结构如球体、环和珠子的形成。我们的结果表明，当F被Y或W取代时，与20%的TFE相比，20%的HFIP更有利于淀粉样纤维的形成。肽在DMSO中溶解，随后溶剂蒸发并在水中溶解，这似乎极大地影响了肽的构象、形态以及自组装结构的交叉β含量。我们的研究表明，芳香族残基F、Y和W的定位在指导肽的自组装中起重要作用。
