文章基本信息

标题：β-barrel Oligomers as Common Intermediates of Peptides Self-Assembling into Cross-β Aggregates
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作者：Yunxiang Sun ; Xinwei Ge ; Yanting Xing 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2018
卷号：8
期号：1
页码：10353
DOI：10.1038/s41598-018-28649-7
语种：English
出版社：Springer Nature
摘要：Oligomers populated during the early amyloid aggregation process are more toxic than mature fibrils, but pinpointing the exact toxic species among highly dynamic and heterogeneous aggregation intermediates remains a major challenge. β-barrel oligomers, structurally-determined recently for a slow-aggregating peptide derived from αB crystallin, are attractive candidates for exerting amyloid toxicity due to their well-defined structures as therapeutic targets and compatibility to the "amyloid-pore" hypothesis of toxicity. To assess whether β-barrel oligomers are common intermediates to amyloid peptides - a necessary step toward associating β-barrel oligomers with general amyloid cytotoxicity, we computationally studied the oligomerization and fibrillization dynamics of seven well-studied fragments of amyloidogenic proteins with different experimentally-determined aggregation morphologies and cytotoxicity. In our molecular dynamics simulations, β-barrel oligomers were only observed in five peptides self-assembling into the characteristic cross-β aggregates, but not the other two that formed polymorphic β-rich aggregates as reported experimentally. Interestingly, the latter two peptides were previously found nontoxic. Hence, the observed correlation between β-barrel oligomers formation and cytotoxicity supports the hypothesis of β-barrel oligomers as the common toxic intermediates of amyloid aggregation.