Moving in the Right Direction: Protein Vibrational Steering Function
Moving in the Right Direction: Protein Vibrational Steering Function
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DOI：
10.1016/j.bpj.2016.12.049
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发表时间：
2017-03-14
影响因子：
3.4
通讯作者：
Markelz, Andrea G.
中科院分区：
文献类型：
--
作者：
Niessen, Katherine A.;Xu, Mengyang;Markelz, Andrea G.
几乎所有的蛋白质功能都需要结构变化，如酶与底物的结合，以及离子通道的打开和关闭。这些运动是可能的新疗法的目标;然而，控制机制仍在争论中。计算表明，蛋白质振动使结构变化。然而，先前的测量发现这些振动仅微弱地依赖于功能状态。通过使用各向异性太赫兹显微镜的新技术，我们发现抑制剂与溶菌酶结合时振动方向性发生了显着变化，而通过中子非弹性散射测量的振动能量分布仅发生轻微改变。各向异性太赫兹测量提供了对分子内振动方向性的独特访问，并立即解决了计算和先前测量之间的不一致性，这些测量仅对能量分布敏感。振动方向与能量分布的生物学重要性，揭示了我们的计算比较野生型溶菌酶与一个更高的催化速率双缺失突变体。振动能量分布是相同的，但更有效的突变体显示出明显的运动重新取向。这些结果表明，它是必不可少的，以了解和控制蛋白质动力学的运动方向性，以优化或抑制功能。
Nearly all protein functions require structural change, such as enzymes clamping onto substrates, and ion channels opening and closing. These motions are a target for possible new therapies; however, the control mechanisms are under debate. Calculations have indicated protein vibrations enable structural change. However, previous measurements found these vibrations only weakly depend on the functional state. By using the novel technique of anisotropic terahertz microscopy, we find that there is a dramatic change to the vibrational directionality with inhibitor binding to lysozyme, whereas the vibrational energy distribution, as measured by neutron inelastic scattering, is only slightly altered. The anisotropic terahertz measurements provide unique access to the directionality of the intramolecular vibrations, and immediately resolve the inconsistency between calculations and previous measurements, which were only sensitive to the energy distribution. The biological importance of the vibrational directions versus the energy distribution is revealed by our calculations comparing wild-type lysozyme with a higher catalytic rate double deletion mutant. The vibrational energy distribution is identical, but the more efficient mutant shows an obvious reorientation of motions. These results show that it is essential to characterize the directionality of motion to understand and control protein dynamics to optimize or inhibit function.