...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Measurement of energy landscape roughness of folded and unfolded proteins
【24h】

Measurement of energy landscape roughness of folded and unfolded proteins

机译：折叠和展开蛋白质的能量能级粗糙度测量

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The dynamics of protein conformational changes, from protein folding to smaller changes, such as those involved in ligand binding, are governed by the properties of the conformational energy landscape. Different techniques have been used to follow the motion of a protein over this landscape and thus quantify its properties. However, these techniques often are limited to short timescales and low-energy conformations. Here, we describe a general approach that overcomes these limitations. Starting from a nonnative conformation held by an aromatic disulfide bond, we use time-resolved spectroscopy to observe nonequilibrium backbone dynamics over nine orders of magnitude in time, from picoseconds to milliseconds, after photolysis of the disulfide bond. We find that the reencounter probability of residues that initially are in close contact decreases with time following an unusual power law that persists over the full time range and is independent of the primary sequence. Model simulations show that this power law arises from subdiffusional motion, indicating a wide distribution of trapping times in local minima of the energy landscape, and enable us to quantify the roughness of the energy landscape (4-5 k_BT). Surprisingly, even under denaturing conditions, the energy landscape remains highly rugged with deep traps (>20 k_BT) that result from multiple nonnative interactions and are sufficient for trapping on the millisecond timescale. Finally, we suggest that the subdiffusional motion of the protein backbone found here may promote rapid folding of proteins with low contact order by enhancing contact formation between nearby residues.
机译：从蛋白质折叠到较小的变化（例如与配体结合有关的变化）的蛋白质构象变化的动力学受构象能量格局的特性支配。已经使用了不同的技术来跟踪蛋白质在此环境中的运动，从而量化其性质。但是，这些技术通常仅限于较短的时间范围和低能耗的构象。在这里，我们描述了克服这些限制的通用方法。从芳族二硫键所持的非天然构象开始，我们使用时间分辨光谱法，在二硫键光解后，从皮秒到毫秒，在九个数量级的时间内观察非平衡主链动力学。我们发现，最初遵循紧密联系的残基的再遇到概率会随着时间的推移而降低，这是遵循不寻常的幂定律的，该定律在整个时间范围内都保持不变，并且与主序列无关。模型仿真表明，该幂律是由次扩散运动引起的，表明在能量分布图的局部极小值中捕获时间分布较宽，使我们能够量化能量分布图的粗糙度（4-5 k_BT）。出乎意料的是，即使在变性条件下，能量格局仍然高度崎with不安，因为深陷陷阱（> 20 k_BT）是由多种非本征相互作用产生的，足以捕获毫秒级的时标。最后，我们建议此处发现的蛋白质骨架的亚扩散运动可能会通过增强附近残基之间的接触形成来促进具有低接触顺序的蛋白质快速折叠。

著录项

  • 来源
  • 作者

    Lilia Milanesi; Jonathan P. Waltho; Christopher A. Hunter; Daniel J. Shaw; Godfrey S. Beddard; Gavin D. Reid; Sagarika Dev; Martin VoIk;

  • 作者单位

    Departments of Molecular Biology and Biotechnology , University of Sheffield, Sheffield S10 2TN, United Kingdom Departments of Chemistry, University of Sheffield, Sheffield S10 2TN, United Kingdom;

    Departments of Molecular Biology and Biotechnology , University of Sheffield, Sheffield S10 2TN, United Kingdom Manchester Institute of Biotechnology, Manchester M1 7DN, United Kingdom;

    Departments of Chemistry, University of Sheffield, Sheffield S10 2TN, United Kingdom;

    School of Chemistry, University of Leeds, Leeds LS2 9JT, United Kingdom;

    School of Chemistry, University of Leeds, Leeds LS2 9JT, United Kingdom;

    School of Chemistry, University of Leeds, Leeds LS2 9JT, United Kingdom;

    Department of Chemistry, University of Liverpool, Liverpool L69 3BX, United Kingdom;

    Department of Chemistry, University of Liverpool, Liverpool L69 3BX, United Kingdom;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    photochemical trigger; subdiffusion;

    机译：光化学触发子扩散;

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号