Pressure-dependent changes in the solution structure of hen egg-white lysozyme.
Pressure-dependent changes in the solution structure of hen egg-white lysozyme.
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DOI：
10.1016/s0022-2836(03)00209-2
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发表时间：
2003-04
影响因子：
5.6
通讯作者：
M. Refaee;T. Tezuka;K. Akasaka;M. Williamson
中科院分区：
文献类型：
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作者：
M. Refaee;T. Tezuka;K. Akasaka;M. Williamson
蛋白质结构和稳定性的“规则”仍然知之甚少。重要的线索来自于在极端条件下工作的蛋白质，因为这些蛋白质澄清了蛋白质的物理约束。一个明显的极端是压力，但到目前为止，人们对蛋白质在压力下的行为知之甚少，主要是由于技术原因。因此，我们开发了新的方法来计算溶液中的结构变化与压力，使用NMR化学位移的变化，我们报告的结构变化的溶菌酶从30巴到2000巴，这是第一个溶液结构的球状蛋白质在压力下。由于螺旋之间的紧密堆积，α-螺旋结构域被压缩约1%。域间区域也被压缩。相比之下，β折叠结构域显示出非常小的整体压缩，但比α结构域经历更多的结构变形。最大的体积变化往往发生在接近水化腔。由于等温压缩性与体积波动有关，这表明在常压下，埋藏的水分子在构象波动中起着重要作用，并且被认为是导致压力变性或通道开放的结构变化的成核位点。
The “rules” governing protein structure and stability are still poorly understood. Important clues have come from proteins that operate under extreme conditions, because these clarify the physical constraints on proteins. One obvious extreme is pressure, but so far little is known of the behavior of proteins under pressure, largely for technical reasons. We have therefore developed new methodology for calculating structure change in solution with pressure, using NMR chemical shift changes, and we report the change in structure of lysozyme on going from 30bar to 2000bar, this being the first solution structure of a globular protein under pressure. The α-helical domain is compressed by approximately 1%, due to tighter packing between helices. The interdomain region is also compressed. By contrast, the β-sheet domain displays very little overall compression, but undergoes more structural distortion than the α-domain. The largest volume changes tend to occur close to hydrated cavities. Because isothermal compressibility is related to volume fluctuation, this suggests that buried water molecules play an important role in conformational fluctuation at normal pressures, and are implicated as the nucleation sites for structural changes leading to pressure denaturation or channel opening.