利用示意模型理解$γ$ D-晶体蛋白溶解度倒置的微观基础
Using schematic models to understand the microscopic basis for inverted solubility in $γ$D-crystallin
摘要：
在少数蛋白质中观察到了溶解度倒置--冷却时晶体熔化--如碳氧血红蛋白和$γ$ D-晶状体蛋白。在人$γ$ D-晶状体蛋白中，该现象与23个$^\mathrm{rd}$残基（脯氨酸）突变为苏氨酸、丝氨酸或缬氨酸有关。一种提出的这种效应的微观机制需要在诱变后增加疏水性。最近的晶体结构的双突变体，包括P23 T突变允许更仔细的调查这一建议。在这里，我们首先测量该蛋白质的各种突变结构的表面疏水性，并确定其在突变23个$^\mathrm{rd}$残基后不会明显增加。然后，我们调查的溶解度反转制度与示意性补丁颗粒模型，其中包括三个模型之一的温度依赖性补丁能量：两个疏水效应，和一个更通用的描述。我们的结论是，虽然由于疏水效应的溶解度反转可能是可能的，微观证据支持它在$γ$ D-晶状体蛋白是弱的。更一般地说，我们发现，溶解度反转需要补丁强度和温度依赖性的贡献之间的良好平衡，这可以解释为什么反转的溶解度是不常见的蛋白质。在任何情况下，我们还发现，温度依赖性的相互作用只有一个可以忽略不计的影响的关键属性的$γ$ D-晶体蛋白，与以前的实验观察。
英文摘要：
Inverted solubility--a crystal melting upon cooling--is observed in a handful of proteins, such as carbomonoxy hemoglobin and $γ$D-crystallin. In human $γ$D-crystallin, the phenomenon is associated with the mutation of the 23$^\mathrm{rd}$ residue, a proline, to a threonine, serine or valine. One proposed microscopic mechanism for this effect entails an increase in hydrophobicity upon mutagenesis. Recent crystal structures of a double mutant that includes the P23T mutation allows for a more careful investigation of this proposal. Here, we first measure the surface hydrophobicity of various mutant structures of this protein and determine that it does not discernibly increase upon the mutating the 23$^\mathrm{rd}$ residue. We then investigate the solubility inversion regime with a schematic patchy particle model that includes one of three models for temperature-dependent patch energies: two of the hydrophobic effect, and a more generic description. We conclude that while solubility inversion due to the hydrophobic effect may be possible, microscopic evidence to support it in $γ$D-crystallin is weak. More generally, we find that solubility inversion requires a fine balance between patch strengths and the temperature-dependent contribution, which may explain why inverted solubility is not commonly observed in proteins. In any event, we also find that the temperature-dependent interaction has only a negligible impact on the critical properties of the $γ$D-crystallin, in line with previous experimental observations.
机构、总结、中文摘要均由AI分析而来，可能存在错误，请以论文正文为准。
