Mechanically induced titin kinase activation studied by force-probe molecular dynamics simulations
文献类型：期刊论文
| 作者 | Grater, F; Shen, JH ; Jiang, HL; Gautel, M; Grubmuller, H
|
| 刊名 | BIOPHYSICAL JOURNAL
 |
| 出版日期 | 2005-02 |
| 卷号 | 88期号:2页码:790-804 |
| ISSN号 | 0006-3495 |
| DOI | 10.1529/biophysj.104.052423 |
| 文献子类 | Article |
| 英文摘要 | The conversion of mechanical stress into a biochemical signal in a muscle cell requires a force sensor. Titin kinase, the catalytic domain of the elastic muscle protein titin, has been suggested as a candidate. Its activation requires major conformational changes resulting in the exposure of its active site. Here, force-probe molecular dynamics simulations were used to obtain insight into the tension-induced activation mechanism. We find evidence for a sequential mechanically induced opening of the catalytic site without complete domain unfolding. Our results suggest the rupture of two terminal beta-sheets as the primary unfolding steps. The low force resistance of the C-terminal relative to the N-terminal beta-sheet is attributed to their different geometry. A subsequent rearrangement of the autoinhibitory tail is seen to lead to the exposure of the active site, as is required for titin kinase activity. These results support the hypothesis of titin kinase as a force sensor. |
| WOS关键词 | MUSCLE PROTEIN TITIN ; IMMUNOGLOBULIN DOMAINS ; CATALYTIC SUBUNIT ; CRYSTAL-STRUCTURE ; STRUCTURAL BASIS ; CARDIAC TITIN ; IG DOMAIN ; M-LINE ; SPECTROSCOPY ; ELASTICITY |
| WOS研究方向 | Biophysics |
| 语种 | 英语 |
| WOS记录号 | WOS:000226750800007 |
| 出版者 | BIOPHYSICAL SOCIETY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/273919]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Grubmuller, H |
| 作者单位 | 1.Kings Coll London, Randall Div, London SE1 1UL, England 2.Max Planck Inst Biophys Chem, Theoret & Computat Biophys Dept, D-37077 Gottingen, Germany 3.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China 4.Kings Coll London, Cardiovasc Res Div, London SE1 1UL, England |
| 推荐引用方式 GB/T 7714 | Grater, F,Shen, JH,Jiang, HL,et al. Mechanically induced titin kinase activation studied by force-probe molecular dynamics simulations[J]. BIOPHYSICAL JOURNAL,2005,88(2):790-804. |
| APA | Grater, F,Shen, JH,Jiang, HL,Gautel, M,&Grubmuller, H.(2005).Mechanically induced titin kinase activation studied by force-probe molecular dynamics simulations.BIOPHYSICAL JOURNAL,88(2),790-804. |
| MLA | Grater, F,et al."Mechanically induced titin kinase activation studied by force-probe molecular dynamics simulations".BIOPHYSICAL JOURNAL 88.2(2005):790-804. |
入库方式： OAI收割
来源：上海药物研究所
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