Wu Guang, Yan Shaomin
Laboratoire de Toxicocinétique et Pharmacocinétique, Faculté de Pharmacie, Université de la Méditerranée Aix-Marseille II, Marseille, France.
J Biochem Mol Biol Biophys. 2002 Dec;6(6):401-6. doi: 10.1080/1025814021000036142.
In this data-based theoretical analysis, we use the random approach to analyse the amino acid pairs in human low-density lipoprotein receptor (LDL receptor) precursor in order to determine which amino acid pairs are more sensitive to 127 variants from missense mutant human LDL receptor. The rationale of this study is based on our hypothesis and findings that the harmful variants are more likely to occur at randomly unpredictable amino acid pairs, the unharmful variants are more likely to occur at randomly predictable amino acid pairs. This is because we argue that the randomly predictable amino acid pairs should not be deliberately evolved, whereas the randomly unpredictable amino acid pairs should be deliberately evolved with connection of protein function. The results show, for examples, 96.06% of 127 variants occur at randomly unpredictable amino acid pairs, which account for 80.44% of amino acid pairs in LDL receptor, and the chance of occurring of variant is about five times higher in randomly unpredictable amino acid pairs than in predictable pairs. Thus, the randomly unpredictable amino acid pairs are more sensitive to variants in human LDL receptor. The results also suggest that the human LDL receptor has the natural tendency to variants.
在这项基于数据的理论分析中，我们采用随机方法分析人类低密度脂蛋白受体（LDL受体）前体中的氨基酸对，以确定哪些氨基酸对对错义突变型人类LDL受体的127个变体更为敏感。本研究的基本原理基于我们的假设和发现，即有害变体更有可能出现在随机不可预测的氨基酸对上，无害变体更有可能出现在随机可预测的氨基酸对上。这是因为我们认为随机可预测的氨基酸对不应被刻意进化，而随机不可预测的氨基酸对应与蛋白质功能相关联进行刻意进化。例如，结果显示，127个变体中的96.06%出现在随机不可预测的氨基酸对上，这些氨基酸对占LDL受体中氨基酸对的80.44%，随机不可预测的氨基酸对中变体出现的几率比可预测的氨基酸对高出约五倍。因此，随机不可预测的氨基酸对对人类LDL受体中的变体更为敏感。结果还表明，人类LDL受体具有变体的自然倾向。
