...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochemistry >Temperature and urea have opposing impacts on polyproline II conformational Bias
【24h】

Temperature and urea have opposing impacts on polyproline II conformational Bias

机译：温度和尿素对聚脯氨酸II构象偏倚有相反的影响

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 native states of globular proteins have been accessed in atomic detail by X-ray crystallography and nuclear magnetic resonance spectroscopy, yet characterization of denatured proteins beyond global metrics has proven to be elusive. Denatured proteins have been observed to exhibit global geometric properties of a random coil polymer. However, this does not preclude the existence of nonrandom, local conformational bias that may be significant for protein folding and function. Indeed, circular dichroism (CD) spectroscopy and other methods have suggested that the denatured state contains considerable local bias to the polyproline II (PII) conformation. Here, we develop predictive models to determine the extent that temperature and the chemical denaturant urea modulate PII propensity. In agreement with our predictive model, PII propensity is observed experimentally to decrease with an increase in temperature. Conversely, urea appears to promote the PII conformation as determined by CD and isothermal titration calorimetry. Importantly, the calorimetric data are in quantitative agreement with a model that predicts the stability of the PII helix relative to other denatured state conformations based upon solvent accessible surface area and experimentally measured Gibbs transfer free energies. The ability of urea to promote the PII conformation can be attributed to the favorable interaction of urea with the peptide backbone. Thus, perturbing denatured states by temperature or cosolutes has subtle, yet opposing, impacts on local PII conformational biases. These results have implications for protein folding as well as for the function of signaling proteins that bind proline-rich targets in globular or intrinsically disordered proteins.
机译：X射线晶体学和核磁共振波谱已详细地了解了球形蛋白质的天然状态，但事实证明，对变性蛋白质的表征超出了全球范围，已难以捉摸。已经观察到变性蛋白质表现出无规卷曲聚合物的整体几何性质。但是，这并不排除存在非随机性，局部构象偏差，这可能对蛋白质折叠和功能很重要。确实，圆二色性（CD）光谱法和其他方法表明变性状态包含对聚脯氨酸II（PII）构象的相当大的局部偏差。在这里，我们建立了预测模型，以确定温度和化学变性尿素调节PII倾向的程度。与我们的预测模型相符，实验观察到PII倾向随温度升高而降低。相反，如通过CD和等温滴定量热法测定的，尿素似乎可以促进PII构象。重要的是，量热数据与基于溶剂可及表面积和实验测得的吉布斯转移自由能预测PII螺旋​​相对于其他变性态构象的稳定性的模型在定量上吻合。尿素促进PII构象的能力可以归因于尿素与肽主链的有利相互作用。因此，通过温度或固溶体扰动变性态对局部PII构象偏倚有微妙但相反的影响。这些结果对蛋白质折叠以及与球形或内在无序蛋白质中富含脯氨酸的靶标结合的信号传导蛋白质的功能具有影响。

著录项

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