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SARS-CoV-2 的位点特异性糖基化:质谱分析中的重大挑战。

Site-specific glycosylation of SARS-CoV-2: Big challenges in mass spectrometry analysis.

机构信息

Max-Planck-Institut fuer Herz- und Lungenforschung, Bad Nauheim, Germany.

Department of Bioengineering, Volgenau School of Engineering and Computing, George Mason University, Fairfax, Virginia, USA.

出版信息

Proteomics. 2022 Aug;22(15-16):e2100322. doi: 10.1002/pmic.202100322. Epub 2022 Jun 22.

DOI:10.1002/pmic.202100322
PMID:35700310
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9349404/
Abstract

Glycosylation of viral proteins is required for the progeny formation and infectivity of virtually all viruses. It is increasingly clear that distinct glycans also play pivotal roles in the virus's ability to shield and evade the host's immune system. Recently, there has been a great advancement in structural identification and quantitation of viral glycosylation, especially spike proteins. Given the ongoing pandemic and the high demand for structure analysis of SARS-CoV-2 densely glycosylated spike protein, mass spectrometry methodologies have been employed to accurately determine glycosylation patterns. There are still many challenges in the determination of site-specific glycosylation of SARS-CoV-2 viral spike protein. This is compounded by some conflicting results regarding glycan site occupancy and glycan structural characterization. These are probably due to differences in the expression systems, form of expressed spike glycoprotein, MS methodologies, and analysis software. In this review, we recap the glycosylation of spike protein and compare among various studies. Also, we describe the most recent advancements in glycosylation analysis in greater detail and we explain some misinterpretation of previously observed data in recent publications. Our study provides a comprehensive view of the spike protein glycosylation and highlights the importance of consistent glycosylation determination.

摘要

糖基化是病毒蛋白翻译后修饰的重要方式之一,几乎所有病毒的子代形成和感染性都需要糖基化。越来越多的证据表明,不同的聚糖在病毒躲避宿主免疫系统方面也起着关键作用。最近,在病毒糖基化结构鉴定和定量方面取得了很大进展,特别是在刺突蛋白方面。鉴于当前的大流行以及对 SARS-CoV-2 高度糖基化刺突蛋白结构分析的高需求,质谱方法已被用于准确确定糖基化模式。在确定 SARS-CoV-2 病毒刺突蛋白的位点特异性糖基化方面仍然存在许多挑战。这是由于关于聚糖位点占有率和聚糖结构特征的一些相互矛盾的结果造成的。这些可能是由于表达系统、表达的刺突糖蛋白形式、MS 方法和分析软件的差异造成的。在这篇综述中,我们总结了刺突蛋白的糖基化,并比较了不同研究之间的差异。此外,我们还更详细地描述了糖基化分析的最新进展,并解释了最近出版物中对先前观察到的数据的一些误解。我们的研究提供了对刺突蛋白糖基化的全面了解,并强调了一致的糖基化确定的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f459/9349404/57437f1251a3/PMIC-22-0-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f459/9349404/2d0eafb64aaf/PMIC-22-0-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f459/9349404/3c67a14687a8/PMIC-22-0-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f459/9349404/aba133cd3678/PMIC-22-0-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f459/9349404/ce4fbad79966/PMIC-22-0-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f459/9349404/de3393cb71d1/PMIC-22-0-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f459/9349404/57437f1251a3/PMIC-22-0-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f459/9349404/2d0eafb64aaf/PMIC-22-0-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f459/9349404/3c67a14687a8/PMIC-22-0-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f459/9349404/aba133cd3678/PMIC-22-0-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f459/9349404/ce4fbad79966/PMIC-22-0-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f459/9349404/de3393cb71d1/PMIC-22-0-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f459/9349404/57437f1251a3/PMIC-22-0-g001.jpg

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