Principles underlying energetic coupling along an allosteric communication trajectory of a voltage-activated K+ channel
Principles underlying energetic coupling along an allosteric communication trajectory of a voltage-activated K+ channel
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DOI：
10.1073/pnas.0708120104
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发表时间：
2007-12-11
影响因子：
11.1
通讯作者：
Yifrach, Ofer
中科院分区：
文献类型：
--
作者：
Sadovsky, Evgeniya;Yifrach, Ofer
蛋白质远端元件之间的信息流可能依赖于沿着蛋白质三级或四级结构的变构通讯轨迹。为了揭示电压门控 K+ 通道中沿变构途径能量解析的基本特征，进行了高阶热力学耦合分析。我们报告说，这种变构轨迹在功能上是保守的，并由明确的边界描绘。此外，变构轨迹呈现分层组织，由此越来越强的协作残基相互作用层发挥作用，以确保远端通道区域之间有效且协作的长程耦合。这种长距离通讯是由局部和整体构象变化的耦合带来的，这表明变构轨迹也对应于物理变形的路径。在理论分析和类比研究分析长程残基偶联对蛋白质稳定性的贡献的支持下，我们提出这种实验得出的轨迹特征是变构调节蛋白质的一般特性。
The information flow between distal elements of a protein may rely on allosteric communication trajectories lying along the protein's tertiary or quaternary structure. To unravel the underlying features of energy parsing along allosteric pathways in voltage-gated K+ channels, high-order thermodynamic coupling analysis was performed. We report that such allosteric trajectories are functionally conserved and delineated bywell defined boundaries. Moreover, allosteric trajectories assume a hierarchical organization whereby increasingly stronger layers of cooperative residue interactions act to ensure efficient and cooperative long-range coupling between distal channel regions. Such long-range communication is brought about by a coupling of local and global conformational changes, suggesting that the allosteric trajectory also corresponds to a pathway of physical deformation. Supported by theoretical analyses and analogy to studies analyzing the contribution of long-range residue coupling to protein stability, we propose that such experimentally derived trajectory features are a general property of allosterically regulated proteins.