Case Study of Hydrogen Bonding in a Hydrophobic Cavity
Case Study of Hydrogen Bonding in a Hydrophobic Cavity
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DOI：
10.1021/jp5097053
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发表时间：
2014-12-18
影响因子：
3.3
通讯作者：
Sue, Shih-Che
中科院分区：
文献类型：
--
作者：
Chen, Yi-Chen;Cheng, Chao-Sheng;Sue, Shih-Che
蛋白质内部氢键和疏水性决定了蛋白质的折叠和结构稳定性，氢键的引入被认为是蛋白质结构巩固的更好的相互作用。我们观察到鸡IL-1 β的另一个例子。天然IL-1 β在Y157侧链O eta H和I133主链CO之间含有一个氢键，因此从Tyr到Phe的取代消除了这种连接，没有氢键的突变体更稳定。当只考虑几乎相同的x射线结构时，试图解释氢键存在的能量观点失败了。在这里，我们通过监测蛋白质骨架动力学和内部氢键网络来解决机制。IL-1b蛋白内部含有一个疏水空腔，Y157是其周围的残基之一。Y157 O eta H基团在疏水腔中引入了不利的能量，因此通过与邻近残基I133形成氢键来隔离自身。氢键限制了Y157的取向，但施加了一个力来破坏围绕空腔的氢键网络。通过核磁共振氢-氘（H/D）交换实验观察到的蛋白质骨架动力学反映了这种效应在整个蛋白质上传播并降低了稳定性。我们描述的特殊情况下，氢键不一定赋予增强蛋白质的稳定性，而必须全面考虑疏水性的破坏。
Protein internal hydrogen bonds and hydrophobicity determine protein folding and structure stabilization, and the introduction of a hydrogen bond has been believed to represent a better interaction for consolidating protein structure. We observed an alternative example for chicken IL-1 beta. The native IL-1 beta contains a hydrogen bond between the Y157 side-chain O eta H and I133 backbone CO, whereby the substitution from Tyr to Phe abolishes the connection and the mutant without the hydrogen bond is more stable. An attempt to explain the energetic view of the presence of the hydrogen bond fails when only considering the nearly identical X-ray structures. Here, we resolve the mechanism by monitoring the protein backbone dynamics and interior hydrogen bond network. IL-1b contains a hydrophobic cavity in the protein interior, and Y157 is one of the surrounding residues. The Y157 O eta H group introduces an unfavorable energy in the hydrophobic cavity, therefore sequestering itself by forming a hydrogen bond with the proximate residue I133. The hydrogen bonding confines Y157 orientation but exerts a force to disrupt the hydrogen bond network surrounding the cavity. The effect propagates over the entire protein and reduces the stability, as reflected in the protein backbone dynamics observed by an NMR hydrogen-deuterium (H/D) exchange experiment. We describe the particular case in which a hydrogen bond does not necessarily confer enhanced protein stability while the disruption of hydrophobicity must be integrally considered.