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化学交联-质谱(CXL-MS)在蛋白质组学、抗体药物偶联物(ADCs)和冷冻电子显微镜(cryo-EM)中的应用。

Chemical Crosslinking-Mass Spectrometry (CXL-MS) for Proteomics, Antibody-Drug Conjugates (ADCs) and Cryo-Electron Microscopy (cryo-EM).

机构信息

Amity University Haryana, Manesar, Haryana, India.

SASTRA Deemed to be University, Thanjavur, Tamil Nadu, India.

出版信息

IUBMB Life. 2018 Oct;70(10):947-960. doi: 10.1002/iub.1916. Epub 2018 Sep 3.

DOI:10.1002/iub.1916
PMID:30176115
Abstract

Chemical crosslinking-mass spectrometry (CXL-MS) has emerged as a powerful tool in structural biology to elucidate protein-protein interactions. This review throws light on the advent of these technologies incorporating chemical crosslinking in proteomics, structural biology and extended to studies and applications of antibody-drug conjugates (ADCs). Monoclonal ASCs are known to target their specific receptors, where the drug could be released for vastly improved therapeutic effect. Cryo-electron microscopy (cryo-EM) is being referred to as the "revolution of the century" as it can help attain almost atomic resolution, while preserving the biological samples at near-native state and has been recognized by the Nobel award 2017. CXL-MS and appropriate bioinformatics tools in combination with cryo-EM reveal better 3D information about dynamic interactions in proteins, interactive domains and motifs, among others in ADCs and in viruses like Zika virus, Rota virus, Dengue virus and also spliceosomes at resolutions, especially below 3 Å. © 2018 IUBMB Life, 70(10):947-960, 2018.

摘要

化学交联-质谱(CXL-MS)已成为结构生物学中阐明蛋白质-蛋白质相互作用的有力工具。这篇综述介绍了这些技术的出现,包括蛋白质组学、结构生物学中的化学交联,以及扩展到抗体药物偶联物(ADC)的研究和应用。单克隆 ASC 已知可以靶向其特定受体,药物可以在那里释放,从而获得大大改善的治疗效果。低温电子显微镜(cryo-EM)被称为“世纪的革命”,因为它可以帮助达到几乎原子分辨率,同时将生物样本保存在接近天然状态,并在 2017 年获得诺贝尔奖认可。CXL-MS 和适当的生物信息学工具与 cryo-EM 结合,可以揭示 ADC 中蛋白质、相互作用域和基序等动态相互作用的更好的 3D 信息,以及寨卡病毒、轮状病毒、登革热病毒等病毒,以及剪接体的分辨率,特别是低于 3 Å。©2018 IUBMB Life,70(10):947-960,2018。

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