Varied Probability of Staying Collapsed/Extended at the Conformational Equilibrium of Monomeric A beta(40) and A beta(42)
文献类型：期刊论文
| 作者 | Song, Wanling1; Wang, Yuanyuan1; Colletier, Jacques-Philippe2,3,4; Yang, Huaiyu1; Xu, Yechun1
|
| 刊名 | SCIENTIFIC REPORTS
 |
| 出版日期 | 2015-06-05 |
| 卷号 | 5 |
| ISSN号 | 2045-2322 |
| DOI | 10.1038/srep11024 |
| 文献子类 | Article |
| 英文摘要 | In present study, we set out to investigate the conformation dynamics of A beta(40) and A beta(42) through exploring the impact of intra-molecular interactions on conformation dynamics using equilibrium molecular dynamics simulations. Our 40 microsecond-scale simulations reveal heterogeneous conformation ensembles of A beta(40) and A beta(42) that encompass similar to 35% beta-strand and similar to 60% unstructured coils. Two conformational states were identified in both alloforms: a collapsed state (CS) that resembles the structural motif of face-to-face hydrophobic clustering in amyloid fibrils, and an extended state (ES) that features the structural characteristics of anti-parallel beta-sheets in amyloid oligomers. In A beta(40), the C-terminus remains unstructured and rarely interacts with other parts, thereof the hydrophobic clustering is in loose contact and the peptide assumes ES with high probability. In contrast, the C-terminus of A beta(42) adopts a beta-strand structure that strongly interacts with segments E3-R5 and V18-A21. The active association leads to a more compact hydrophobic collapse and refrain the alloform from ES. Based on the structural characterization, we propose that the fibril and oligomer assembly pathways could respectively take off from CS and ES, and their aggregation propensity may be governed by the probability of visiting the corresponding conformational states at the equilibrium. |
| WOS关键词 | AMYLOID-BETA-PROTEIN ; ALZHEIMERS-DISEASE ; COUPLING-CONSTANTS ; MOLECULAR-DYNAMICS ; SECONDARY STRUCTURE ; COMBINED MD/NMR ; RANDOM COIL ; PEPTIDE ; FIBRILS ; NMR |
| 资助项目 | "100 Talents Project" of CAS[00000000] ; CAS-Novo Nordisk Great Wall Professorship[00000000] ; National Natural Science Foundation of China[91013010] ; National Natural Science Foundation of China[21172233] ; National Natural Science Foundation of China[81422047] ; National Natural Science Foundation of China[31150110578] ; National ST Major Project[2012ZX09301001-005] ; National Supercomputing Center in Tianjin (Tianhe-1)[00000000] ; Computer Network Information Center (CNIC) of the Chinese Academy of Sciences (CAS)[00000000] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000355876400002 |
| 出版者 | NATURE PUBLISHING GROUP |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276495]  |
| 专题 | 药物发现与设计中心 |
| 通讯作者 | Xu, Yechun |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China; 2.CNRS, IBS, F-38044 Grenoble, France; 3.CEA, IBS, F-38044 Grenoble, France 4.Univ Grenoble Alpes, IBS, F-38044 Grenoble, France; |
| 推荐引用方式 GB/T 7714 | Song, Wanling,Wang, Yuanyuan,Colletier, Jacques-Philippe,et al. Varied Probability of Staying Collapsed/Extended at the Conformational Equilibrium of Monomeric A beta(40) and A beta(42)[J]. SCIENTIFIC REPORTS,2015,5. |
| APA | Song, Wanling,Wang, Yuanyuan,Colletier, Jacques-Philippe,Yang, Huaiyu,&Xu, Yechun.(2015).Varied Probability of Staying Collapsed/Extended at the Conformational Equilibrium of Monomeric A beta(40) and A beta(42).SCIENTIFIC REPORTS,5. |
| MLA | Song, Wanling,et al."Varied Probability of Staying Collapsed/Extended at the Conformational Equilibrium of Monomeric A beta(40) and A beta(42)".SCIENTIFIC REPORTS 5(2015). |
入库方式： OAI收割
来源：上海药物研究所
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