Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Protein Sci. 2024 Apr;33(4):e4979. doi: 10.1002/pro.4979.
Proteome diversities and their biological functions are significantly amplified by post-translational modifications (PTMs) of proteins. Shotgun proteomics, which does not typically survey PTMs, provides an incomplete picture of the complexity of human biopsies in health and disease. Recent advances in mass spectrometry-based proteomic techniques that enrich and study PTMs are helping to uncover molecular detail from the cellular level to system-wide functions, including how the microbiome impacts human diseases. Protein heterogeneity and disease complexity are challenging factors that make it difficult to characterize and treat disease. The search for clinical biomarkers to characterize disease mechanisms and complexity related to patient diagnoses and treatment has proven challenging. Knowledge of PTMs is fundamentally lacking. Characterization of complex human samples that clarify the role of PTMs and the microbiome in human diseases will result in new discoveries. This review highlights the key role of proteomic techniques used to characterize unknown biological functions of PTMs derived from complex human biopsies. Through the integration of diverse methods used to profile PTMs, this review explores the genetic regulation of proteoforms, cells of origin expressing specific proteins, and several bioactive PTMs and their subsequent analyses by liquid chromatography and tandem mass spectrometry.
蛋白质的翻译后修饰（PTMs）显著扩增了蛋白质组的多样性及其生物学功能。鸟枪法蛋白质组学通常不会检测 PTMs，因此无法全面了解健康和疾病状态下人体活检的复杂性。基于质谱的蛋白质组学技术的最新进展，可对 PTM 进行富集和研究，有助于从细胞水平到系统功能揭示分子细节，包括微生物组如何影响人类疾病。蛋白质异质性和疾病复杂性是具有挑战性的因素，使得疾病的特征和治疗变得困难。寻找临床生物标志物来描述与患者诊断和治疗相关的疾病机制和复杂性极具挑战性。目前对 PTM 的了解还远远不够。对复杂的人体样本进行特征描述，阐明 PTM 和微生物组在人类疾病中的作用，将带来新的发现。本文重点介绍了蛋白质组学技术在阐明源自复杂人体活检的 PTM 未知生物学功能中的关键作用。通过整合用于分析 PTM 的多种方法，本文探讨了特定蛋白质表达细胞的起源、多种生物活性 PTM 及其随后通过液相色谱和串联质谱进行的分析的遗传调控。
