Multiscaled exploration of coupled folding and binding of an intrinsically disordered molecular recognition element in measles virus nucleoprotein
文献类型：期刊论文
| 作者 | Wang Y ; Chu XK ; Longhi S ; Roche P ; Han W ; Wang EK ; Wang J |
| 刊名 | proceedings of the national academy of sciences of the united states of america
 |
| 出版日期 | 2013 |
| 卷号 | 110期号:40页码:e3743-e3752 |
| 关键词 | C-TERMINAL DOMAIN TRANSITION-STATE ENSEMBLE FLY-CASTING MECHANISM CONFORMATIONAL SELECTION STRUCTURAL DISORDER ENERGY LANDSCAPE EPR SPECTROSCOPY PHYSICAL BASIS RATE CONSTANTS FORCE-FIELD |
| ISSN号 | 0027-8424 |
| 通讯作者 | wang j |
| 中文摘要 | numerous relatively short regions within intrinsically disordered proteins (idps) serve as molecular recognition elements (mores). they fold into ordered structures upon binding to their partner molecules. currently, there is still a lack of in-depth understanding of how coupled binding and folding occurs in mores. here, we quantified the unbound ensembles of the alpha-more within the intrinsically disordered c-terminal domain of the measles virus nucleoprotein. we developed a multiscaled approach by combining a physics-based and an atomic hybrid model to decipher the mechanism by which the alpha-more interacts with the x domain of the measles virus phosphoprotein. our multiscaled approach led to remarkable qualitative and quantitative agreements between the theoretical predictions and experimental results (e.g., chemical shifts). we found that the free alpha-more rapidly interconverts between multiple discrete partially helical conformations and the unfolded state, in accordance with the experimental observations. we quantified the underlying global folding-binding landscape. this leads to a synergistic mechanism in which the recognition event proceeds via (minor) conformational selection, followed by (major) induced folding. we also provided evidence that the alpha-more is a compact molten globule-like idp and behaves as a downhill folder in the induced folding process. we further provided a theoretical explanation for the inherent connections between "downhill folding," "molten globule," and "intrinsic disorder" in idp-related systems. particularly, we proposed that binding and unbinding of idps proceed in a stepwise way through a "kinetic divide-and-conquer" strategy that confers them high specificity without high affinity. |
| 收录类别 | SCI收录期刊论文 |
| 语种 | 英语 |
| WOS记录号 | WOS:000325105500005 |
| 公开日期 | 2014-04-15 |
| 源URL | [http://ir.ciac.jl.cn/handle/322003/49581]  |
| 专题 | 长春应用化学研究所_长春应用化学研究所知识产出_期刊论文 |
| 推荐引用方式 GB/T 7714 | Wang Y,Chu XK,Longhi S,et al. Multiscaled exploration of coupled folding and binding of an intrinsically disordered molecular recognition element in measles virus nucleoprotein[J]. proceedings of the national academy of sciences of the united states of america,2013,110(40):e3743-e3752. |
| APA | Wang Y.,Chu XK.,Longhi S.,Roche P.,Han W.,...&Wang J.(2013).Multiscaled exploration of coupled folding and binding of an intrinsically disordered molecular recognition element in measles virus nucleoprotein.proceedings of the national academy of sciences of the united states of america,110(40),e3743-e3752. |
| MLA | Wang Y,et al."Multiscaled exploration of coupled folding and binding of an intrinsically disordered molecular recognition element in measles virus nucleoprotein".proceedings of the national academy of sciences of the united states of america 110.40(2013):e3743-e3752. |
入库方式： OAI收割
来源：长春应用化学研究所
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