Sadovsky Evgeniya, Yifrach Ofer
Department of Life Sciences and Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel.
Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19813-8. doi: 10.1073/pnas.0708120104. Epub 2007 Dec 5.
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 by well 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.
蛋白质远端元件之间的信息流可能依赖于沿蛋白质三级或四级结构的变构通讯轨迹。为了揭示电压门控钾通道变构途径中能量解析的潜在特征，我们进行了高阶热力学耦合分析。我们报告称，这种变构轨迹在功能上是保守的，并由明确的边界划定。此外，变构轨迹呈现出一种层次结构，即越来越强的协同残基相互作用层起到确保通道远端区域之间高效协同的长程耦合的作用。这种长程通讯是由局部和全局构象变化的耦合实现的，这表明变构轨迹也对应于物理变形的途径。在理论分析以及与分析长程残基耦合对蛋白质稳定性贡献的研究类比的支持下，我们提出，这种通过实验得出的轨迹特征是变构调节蛋白的普遍特性。
