Intrinsic Disorder in the Human Tear Proteome.
Intrinsic Disorder in the Human Tear Proteome.
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DOI：
10.1167/iovs.64.11.14
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发表时间：
2023-08-01
影响因子：
4.4
通讯作者：
中科院分区：
文献类型：
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作者：
我们的目的是表征人类眼泪的蛋白质组，并评估内在无序蛋白（IDPs）的存在。尽管IDPs缺乏刚性的三维结构，但仍保持生物功能，并可能阐明泪液中的分子相互作用。我们分析了三个健康受试者泪膜中鉴定的1475个蛋白质的数据集。我们使用了几种计算工具，包括成分分析器、快速内在紊乱分析在线、相互作用基因检索搜索工具和无序蛋白质预测数据库来评估该蛋白质组内的内在紊乱、蛋白质相互作用和无序区域的功能表征。我们的分析显示出内在无序的显著倾向。10个促序残基中有2个富集，10个促序残基中有5个富集。使用自然无序区预测器（PONDR） VSL2输出，95%的这些蛋白质被分类为高度或中度无序。我们发现了一个广泛的蛋白质相互作用网络，具有显著的相互作用富集。与最有序的蛋白质相比，最无序的蛋白质具有更高的无序结合位点和多种翻译后修饰。据我们所知，我们的研究是第一个对人类泪膜蛋白质组内在紊乱的综合分析，它揭示了丰富的IDPs及其在蛋白质功能和相互作用网络中的作用。这些发现表明，泪膜内在紊乱的变化可能受到系统和眼部疾病的影响，为疾病生物标志物鉴定和药物靶点开发提供了有希望的途径。需要进一步的研究来了解这些发现对人类健康和疾病的影响。
We aimed to characterize the proteome of human tears and assess for the presence of intrinsically disordered proteins (IDPs). IDPs, despite lacking a rigid three-dimensional structure, maintain biological functionality and could shed light on the molecular interactions within tears. We analyzed a dataset of 1475 proteins identified in the tear film of three healthy subjects. We employed several computational tools, including the Compositional Profiler, Rapid Intrinsic Disorder Analysis Online, Search Tool for the Retrieval of Interacting Genes, and Database of Disordered Protein Predictors to evaluate the intrinsic disorder, protein interactions, and functional characterization of the disordered regions within this proteome. Our analysis showed a notable inclination toward intrinsic disorder. Two out of 10 order-promoting residues and five out of 10 disorder-promoting residues were found enriched. Using the Predictor of Natural Disordered Regions (PONDR) VSL2 output, 95% of these proteins were classified as highly or moderately disordered. We revealed an extensive protein–protein interaction network with significant interaction enrichment. The most disordered proteins exhibited higher disorder binding sites and diverse posttranslational modifications compared to the most ordered ones. To the best of our knowledge, our study is the first comprehensive analysis of intrinsic disorder in the human tear film proteome, and it revealed an abundance of IDPs and their role in protein function and interaction networks. These findings suggest that variations in the intrinsic disorder of a tear film could be impacted by systemic and ocular conditions, offering promising avenues for disease biomarker identification and drug target development. Further research is needed to understand the implications of these findings in human health and disease.