两个不同年龄段人血浆蛋白质组的整体化学修饰比较
首发时间:2020-02-13
摘要:蛋白质的化学修饰是指其氨基酸残基或其链末端上参与的共价基团反应,进而使其分子的结构、执行的调控和信息传递的功能得到改变。本研究采用LC-MS/MS技术结合非限制性修饰鉴定算法,比较两组不同年龄阶段人血浆蛋白质组整体的化学修饰水平之间的差异。研究发现在年长组中半胱氨酸的琥珀酰化、磷酸化修饰以及赖氨酸替换为苏氨酸的修饰显著高于年轻组,而赖氨酸的氨甲酰化修饰低于年轻组。半胱氨酸残基中的巯基是形成二硫键、维持蛋白质结构的重要基团,而以上与半胱氨酸相关的修饰涉及巯基的参与。赖氨酸为碱性氨基酸,其氨基上的修饰会改变蛋白质的酸碱性,可能导致蛋白质的结构与功能受到影响。综上所述,本研究在不同年龄段人群血浆蛋白质组中找到4种有显著差异的蛋白质分子修饰与替换类型,推测年长者血液中具有某种修饰蛋白的增多,可能反映出血中失去正常功能的蛋白质增加,这或许是年长者患有代谢性疾病、肿瘤等相关老年性疾病风险的几率高于年轻人的原因之一。
关键词: 蛋白质组 血浆 化学修饰 串联质谱 非限制性修饰鉴定
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Comparison of global chemical modifications of human plasma proteome at two different age groups
Abstract:The chemical modifications of proteins refer to the covalent group reaction involved in its amino acid residues or chain ends, which in turn change the molecular structure and function. There are many types of molecular modifications in the human plasma proteome, such as phosphorylation, methylation, acetylation, etc. In this study, two groups of human plasma proteome at different age groups were used to compare the global chemical modifications by LC-MS/MS combined with non-limiting modification identification algorithms. A total of 4 molecular modifications were found to have statistical differences, the succinylation and phosphorylation modification of cysteine (Cys, C) and the modification of lysine (Lys, K) modification of lysine with threonine (Thr, T) were significantly higher in the old group than in the young group, while the carbamylation of lysine was lower in the young group. The sulfhydryl in the cysteine residue is an important group to form disulfide bonds and maintain the structure of the protein. All differential cysteine-related modifications may cause structural and functional changes. Lysine is a basic amino acid, and the modification of its amino group will change the charge state of the protein, which may affect the structure and function of the protein. In summary, four types of protein chemical modifications and substitutes were found to be differential in the plasma proteome in different age groups. We speculate that there is an increase in certain modified proteins in the blood of the elderly people which in turn changes the function of those proteins. This may be one of the reasons why elderly people are more likely than young people to be at risk for age-related diseases such as metabolic disease, cerebral and cardiovascular diseases, and cancer.
Keywords: Proteome Plasma Chemical modifications Tandem mass spectrometry Non-limiting modification identification
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两个不同年龄段人血浆蛋白质组的整体化学修饰比较
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