Structural proteomics and protein complexes - special issue.
Structural proteomics and protein complexes - special issue.
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结构蛋白质组学和蛋白质复合物 - 特刊。
DOI：
10.1002/pmic.202000286
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发表时间：
2021
期刊：
影响因子：
3.4
通讯作者：
Cooper HJ
中科院分区：
文献类型：
--
作者：
Cooper HJ
结构蛋白质组学领域包括一系列旨在在全球范围内揭开蛋白质结构奥秘的技术。通过结构蛋白质组学，可以获得关于蛋白质的大量信息，包括它们如何发挥功能以及该功能所必需的相互作用伙伴。结构蛋白质组学技术包括但不限于氢氘交换质谱（MS）、交联MS、离子迁移率MS和天然MS，其由生物信息学和计算建模支持。该领域在二十多年前刚刚出现，从那时起一直在快速增长。最近的科学网搜索这个词显示，1999年有9篇出版物和27篇引文，2020年有725篇出版物，引用次数超过38，000次。在本期特刊中，我们很高兴介绍该领域领先研究人员的四篇研究文章和一份技术简报。Sharon及其同事[1]描述了直接MS在抗体-抗原复合物分析中的应用。这项工作利用了天然MS的一种变体，它能够直接分析来自粗生长培养基的抗体-抗原复合物，利用重组抗体在培养基中积累的事实。作者能够研究各种参数，包括稳定性、亲和力和特异性。这项工作的广泛意义源于治疗性抗体在一系列疾病中的重要性，更具体地说，需要可靠和快速的质量评估。更具体地说，作者证明了直接MS方法，它使分析如此接近生物学，提供了许多好处和潜在的应用。Borchers和同事[2]应用结构蛋白质组学提出了一种潜在的朊病毒蛋白β-寡聚体组装模式。这些病理性寡聚体在朊病毒疾病的发展中起着核心作用。在他们的文章中，作者描述了如何通过交联MS阐明的交联约束通知随后的离散分子动力学模拟，以提供单体和二聚体结构的模型。通过氢氘交换质谱、有限蛋白水解和表面修饰对模型进行了验证。这项工作是一个全面的结构蛋白质组学方法结合了一系列的实验技术和计算机建模应用于一个重要的生物医学挑战的一个很好的示范。
The field of structural proteomics encompasses a range of techniques that aim to unravel the mysteries of protein structure on a global scale. Through structural proteomics, a plethora of information can be obtained about proteins including how they function and the interacting partners essential for that function. Structural proteomics techniques include, but are not limited to, hydrogen deuterium exchange mass spectrometry (MS), cross-linking MS, ion mobility MS and native MS, which are supported by bioinformatics and computational modelling. The field emerged just over two decades ago and has enjoyed a rapid growth ever since. A recent Web of Science search for the term revealed nine publications and 27 citations in 1999, and 725 publications with over 38,000 citations in 2020. In this Special Issue, we are pleased to present four research articles and one technical brief from leading researchers in the field. Sharon and co-workers [1] describe the application of direct MS to the analysis of antibody-antigen complexes. The work makes use of a variant of native MS, which enables direct analysis of the antibody–antigen complex from the crude growth media, taking advantage of the fact that recombinant antibodies accumulate in the media. The authors were able to investigate various parameters including stability, affinity and specificity. The broad significance of this work derives from the importance of therapeutic antibodies in a range of diseases and more specifically the need for reliable and rapid quality assessment. More specifically, the authors demonstrate that the direct MS approach, which brings the analysis so close to the biology, offers many benefits and potential applications.Borchers and co-workers [2] apply structural proteomics to propose a potential mode of assembly of β-oligomers of the prion protein. These pathological oligomers play a central role in the development of prion diseases. In their article, the authors describe how cross-linking constraints elucidated by cross-linking MS informed subsequent discrete molecular dynamic simulations to provide models for monomer and dimer structures. The model was verified by hydrogen deuterium exchange MS, limited proteolysis and surface modification. The work is a great demonstration of a comprehensive structural proteomics approach combining a range of experimental techniques and computer modelling applied to an important biomedical challenge.