首页> 外文期刊>Journal of Molecular Biology >Exploring the minimally frustrated energy landscape of unfolded ACBP
【24h】

Exploring the minimally frustrated energy landscape of unfolded ACBP

机译:探索展开的ACBP的受挫程度最小的能源格局

获取原文
获取原文并翻译 | 示例
           

摘要

The unfolded state of globular proteins is not well described by a simple statistical coil due to residual structural features, such as secondary structure or transiently formed long-range contacts. The principle of minimal frustration predicts that the unfolded ensemble is biased toward productive regions in the conformational space determined by the native structure. Transient long-range contacts, both native-like and non-native-like, have previously been shown to be present in the unfolded state of the four-helix-bundle protein acyl co-enzyme binding protein (ACBP) as seen from both perturbations in nuclear magnetic resonance (NMR) chemical shifts and structural ensembles generated from NMR paramagnetic relaxation data. To study the nature of the contacts in detail, we used paramagnetic NMR relaxation enhancements, in combination with single-point mutations, to obtain distance constraints for the acid-unfolded ensemble of ACBP. We show that, even in the acid-unfolded state, long-range contacts are specific in nature and single-point mutations affect the free-energy landscape of the unfolded protein. Using this approach, we were able to map out concerted, interconnected, and productive long-range contacts. The correlation between the native-state stability and compactness of the denatured state provides further evidence for native-like contact formation in the denatured state. Overall, these results imply that, even in the earliest stages of folding, ACBP dynamics are governed by native-like contacts on a minimally frustrated energy landscape.
机译:由于残留的结构特征(例如二级结构或短暂形成的远程接触),无法通过简单的统计线圈很好地描述球形蛋白的未折叠状态。最小挫败感的原理预测,展开的合奏会偏向于由自然结构确定的构象空间中的生产区域。从两种扰动看,以前的天然和非天然的瞬时远程接触都以四螺旋束蛋白酰基辅酶结合蛋白(ACBP)的未折叠状态存在。核磁共振(NMR)中的化学位移和结构集合是由NMR顺磁弛豫数据生成的。为了详细研究接触的性质,我们结合单点突变使用顺磁性NMR弛豫增强功能,以获取ACBP酸展开整体的距离约束。我们显示,即使在酸未折叠状态下,远距离接触也是自然特有的,单点突变会影响未折叠蛋白的自由能态。使用这种方法,我们能够绘制出协调,相互联系和富有成效的远程联系。原始状态的稳定性和变性状态的紧密度之间的相关性为变性状态下的类似天然的接触形成提供了进一步的证据。总体而言,这些结果表明,即使在折叠的最早阶段,ACBP动力学也受到在最小程度受挫的能源形势下类似原生接触的控制。

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