Hydrophobic, Aromatic, and Electrostatic Interactions Play a Central Role in Amyloid Fibril Formation and Stability
Hydrophobic, Aromatic, and Electrostatic Interactions Play a Central Role in Amyloid Fibril Formation and Stability
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DOI：
10.1021/bi101936c
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发表时间：
2011-03-29
期刊：
影响因子：
2.9
通讯作者：
Serpell, Louise C.
中科院分区：
文献类型：
--
作者：
Marshall, Karen E.;Morris, Kyle L.;Serpell, Louise C.
由肽KFFEAAAKKFFE形成的淀粉样纤维状晶体先前已被表征，并提供了一个理想的模型系统，通过引入特定的取代来检查特定相互作用的重要性。我们发现，任何苯丙氨酸残基的去除完全废除组装能力，而带电残基调节结构内的相互作用，导致替代的纤维状形态。X-射线纤维衍射分析表明，肽分子的基本骨架包装保持不变，而小的变化适应变异体中侧链大小的差异。我们的结论是，即使是非常短的肽是适应性和增加有关淀粉样蛋白多态性的知识。此外，这项工作的影响，我们的理解淀粉样蛋白生成肽的残基组合物的重要性，特别是静电，芳香族和疏水相互作用在淀粉样蛋白组装的作用。
Amyloid-like fibrous crystals formed by the peptide KFFEAAAKKFFE have been previously characterized and provide an ideal model system to examine the importance of specific interactions by introducing specific substitutions. We find that the removal of any phenylalanine residue completely abrogates assembly ability, while charged residues modulate interactions within the structure resulting in alternative fibrillar morphologies. X-ray fiber diffraction analysis reveals that the essential backbone packing of the peptide molecules is maintained, while small changes accommodate differences in side chain size in the variants. We conclude that even very short peptides are adaptable and add to the growing knowledge regarding amyloid polymorphisms. Additionally, this work impacts on our understanding of the importance of residue composition for amyloidogenic peptides, in particular the roles of electrostatic, aromatic, and hydrophobic interactions in amyloid assembly.