Schumacher Katherine N, Dodds Eric D
Department of Chemistry, University of Nebraska - Lincoln, 711 Hamilton Hall, Lincoln, NE, 68588-0304, USA.
Glycoconj J. 2016 Jun;33(3):377-85. doi: 10.1007/s10719-016-9663-5. Epub 2016 Mar 23.
Abnormal glycosylation of proteins is known to be either resultant or causative of a variety of diseases. This makes glycoproteins appealing targets as potential biomarkers and focal points of molecular studies on the development and progression of human ailment. To date, a majority of efforts in disease glycoproteomics have tended to center on either determining the concentration of a given glycoprotein, or on profiling the total population of glycans released from a mixture of glycoproteins. While these approaches have demonstrated some diagnostic potential, they are inherently insensitive to the fine molecular detail which distinguishes unique and possibly disease relevant glycoforms of specific proteins. As a consequence, such analyses can be of limited sensitivity, specificity, and accuracy because they do not comprehensively consider the glycosylation status of any particular glycoprotein, or of any particular glycosylation site. Therefore, significant opportunities exist to improve glycoproteomic inquiry into disease by engaging in these studies at the level of individual glycoproteins and their exact loci of glycosylation. In this concise review, the rationale for glycoprotein and glycosylation site specificity is developed in the context of human disease glycoproteomics with an emphasis on N-glycosylation. Recent examples highlighting disease-related perturbations in glycosylation will be presented, including those involving alterations in the overall glycosylation of a specific protein, alterations in the occupancy of a given glycosylation site, and alterations in the compositional heterogeneity of glycans occurring at a given glycosylation site. Each will be discussed with particular emphasis on how protein-specific and site-specific approaches can contribute to improved discrimination between glycoproteomes and glycoproteins associated with healthy and unhealthy states.
蛋白质糖基化异常已知是多种疾病的结果或病因。这使得糖蛋白成为有吸引力的潜在生物标志物靶点以及人类疾病发生和发展分子研究的重点。迄今为止，疾病糖蛋白质组学的大部分工作往往集中在确定给定糖蛋白的浓度，或分析从糖蛋白混合物中释放的聚糖的总体情况。虽然这些方法已显示出一定的诊断潜力，但它们对区分特定蛋白质独特且可能与疾病相关的糖型的精细分子细节天生不敏感。因此，此类分析的灵敏度、特异性和准确性可能有限，因为它们没有全面考虑任何特定糖蛋白或任何特定糖基化位点的糖基化状态。因此，通过在单个糖蛋白及其确切糖基化位点水平上开展这些研究，在改善对疾病的糖蛋白质组学研究方面存在重大机遇。在这篇简要综述中，在人类疾病糖蛋白质组学背景下阐述了糖蛋白和糖基化位点特异性的基本原理，重点是N - 糖基化。将展示突出糖基化中与疾病相关扰动的近期实例，包括那些涉及特定蛋白质整体糖基化改变、给定糖基化位点占据情况改变以及给定糖基化位点处聚糖组成异质性改变的实例。每个实例都将特别强调蛋白质特异性和位点特异性方法如何有助于更好地区分与健康和不健康状态相关的糖蛋白质组和糖蛋白。
