Slow Motions in the Hydrophobic Core of Chicken Villin Headpiece Subdomain and Their Contributions to Configurational Entropy and Heat Capacity from Solid-State Deuteron NMR Measurements
Slow Motions in the Hydrophobic Core of Chicken Villin Headpiece Subdomain and Their Contributions to Configurational Entropy and Heat Capacity from Solid-State Deuteron NMR Measurements
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DOI：
10.1021/bi201515b
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发表时间：
2011-12-13
期刊：
影响因子：
2.9
通讯作者：
Vold, Robert L.
中科院分区：
文献类型：
--
作者：
Vugmeyster, Liliya;Ostroysky, Dmitry;Vold, Robert L.
我们已经研究了微秒到毫秒的时间尺度动力学在几个关键的疏水核心甲基基团的鸡绒毛头部亚结构域蛋白（HP 36）使用单点标记，氘固态NMR线形分析和计算建模的组合。水合粉末样品的氘线形状主要由旋转异构跳跃，并显示出很大的变化率常数，活化能，和旋转异构人口。位点特异性活化能从6到38 kJ/mol不等。对于某些场地，限制弧上的另一种扩散模式是很重要的。在干燥的样品中，动力学被淬灭。运动模型的参数允许计算的配置熵和热容量，其中，连同速率常数，允许观察的热力学和动力学之间的相互作用的景观图片。在L 69的相对刚性侧链的远端（F47 L和F51 L）和近端（F58 L）位置处的关键苯丙氨酸残基处的突变对减轻该侧链在室温下的刚性具有显著效果，并且证明了疏水核心环境对这种扰动的敏感性。
We have investigated microsecond to millisecond time scale dynamics in several key hydrophobic core methyl groups of chicken villin headpiece subdomain protein (HP36) using a combination of single-site labeling, deuteron solid-state NMR line shape analysis, and computational modeling. Deuteron line shapes of hydrated powder samples are dominated by rotameric jumps and show a large variability of rate constants, activation energies, and rotameric populations. Site-specific activation energies vary from 6 to 38 kJ/mol. An additional mode of diffusion on a restricted arc is significant for some sites. In dry samples, the dynamics is quenched. Parameters of the motional models allow for calculations of configurational entropy and heat capacity, which, together with the rate constants, allow for observation of interplay between thermodynamic and kinetic picture of the landscape. Mutations at key phenylalanine residues at both distal (F47L&F51L) and proximal (F58L) locations to a relatively rigid side chain of L69 have a pronounced effect on alleviating the rigidity of this side chain at room temperature and demonstrate the sensitivity of the hydrophobic core environment to such perturbations.