All-atom structure ensembles of islet amyloid polypeptides determined by enhanced sampling and experiment data restraints
文献类型：期刊论文
| 作者 | Su, Xinyue1,3; Wang, Ke1,2; Liu, Na1,2; Chen, Jiawen1; Li, Yong3; Duan, Mojie1 |
| 刊名 | PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
 |
| 出版日期 | 2019-07-01 |
| 卷号 | 87期号:7页码:541-550 |
| 关键词 | aggregation chemical shift restraint islet amylod polypeptide metadynamics |
| ISSN号 | 0887-3585 |
| DOI | 10.1002/prot.25677 |
| 英文摘要 | Exploring the accurate structure ensembles are critical to understand the functions of intrinsically disordered proteins (IDPs). As a well-known IDP, islet amyloid polypeptide (IAPP) plays important roles in the development of human type II diabetes (T2D). The toxicity of human IAPP (hIAPP) is induced by the amyloidosis of the peptide, however, its aggregation mechanism remains ambiguous. The characterization of structure ensemble of hIAPP, as well as the differences between hIAPP and its non-amyloidogenic homologous such as rat IAPP (rIAPP), would greatly help to illuminate the amyloidosis mechanism of IAPP. In this study, the atomic structure ensembles of hIAPP and rIAPP were characterized by all-atom molecular dynamics (MD) simulations combined with enhanced sampling technology and experiment data restraints. The obtained structure ensembles were firstly compared with those determined by the conventional MD (cMD) and enhanced sampling without experiment data restraints. The results showed that the enhanced sampling and experiment data restraints would improve the simulation accuracy. The transient N-terminal alpha-helix structures were adopted by the sub-states of both hIAPP and rIAPP, however, the C-terminal helical structures were only present on hIAPP. The hydrophobic residues in the amyloid-core region of hIAPP are exposed to the solvent. The structure ensemble differences between hIAPP and rIAPP revealed in this work provide potential explain to the amyloidogenic mechanism and would be helpful for the design of drugs to combat T2D. |
| 资助项目 | National Natural Science Foundation of China[21773298] ; National Natural Science Foundation of China[21403291] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Biophysics |
| 语种 | 英语 |
| WOS记录号 | WOS:000469937400002 |
| 出版者 | WILEY |
| 源URL | [http://202.127.146.157/handle/2RYDP1HH/7941]  |
| 专题 | 中国科学院武汉植物园 |
| 通讯作者 | Li, Yong; Duan, Mojie |
| 作者单位 | 1.Chinese Acad Sci, CAS Key Lab Magnet Resonance Biol Syst, State Key Lab Magnet Resonance & Atom & Mol Phys, Natl Ctr Magnet Resonance Wuhan,Wuhan Inst Phys &, Wuhan, Hubei, Peoples R China 2.Univ Chinese Acad Sci, Dept Chem, Beijing, Peoples R China 3.Cent China Normal Univ, Dept Phys, 152 Luoyu Rd, Wuhan 430079, Hubei, Peoples R China |
| 推荐引用方式 GB/T 7714 | Su, Xinyue,Wang, Ke,Liu, Na,et al. All-atom structure ensembles of islet amyloid polypeptides determined by enhanced sampling and experiment data restraints[J]. PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS,2019,87(7):541-550. |
| APA | Su, Xinyue,Wang, Ke,Liu, Na,Chen, Jiawen,Li, Yong,&Duan, Mojie.(2019).All-atom structure ensembles of islet amyloid polypeptides determined by enhanced sampling and experiment data restraints.PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS,87(7),541-550. |
| MLA | Su, Xinyue,et al."All-atom structure ensembles of islet amyloid polypeptides determined by enhanced sampling and experiment data restraints".PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS 87.7(2019):541-550. |
入库方式： OAI收割
来源：武汉植物园
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