期刊
JOURNAL OF MOLECULAR BIOLOGY
卷 433, 期 4, 页码 -出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2020.166762
关键词
SARS-CoV-2; ACE2; glycosylation; surface plasmon resonance; glycan engineering
资金
- International AIDS Vaccine Initiative (IAVI) - Bill and Melinda Gates Foundation [INV-008352/OPP1153692]
- IAVI Neutralizing Antibody Center through the Collaboration for AIDS Vaccine Discovery - Bill and Melinda Gates Foundation [OPP1196345/INV-008813]
- National Institute for Allergy and Infectious Diseases through the Scripps Consortium for HIV Vaccine Development (CHAVD) [AI144462]
- University of Southampton Coronavirus Response Fund
The severity of SARS-CoV-2 infection varies greatly, but the molecular basis for this variability remains unclear. Differences in glycosylation of target human cells may be a contributing factor. Research shows that the glycosylation state of ACE2 has a subtle impact on interaction with SARS-CoV-2, but overall, it does not significantly influence viral spike binding.
The severity of SARS-CoV-2 infection is highly variable and yet the molecular basis for this effect remains elusive. One potential contribution are differences in the glycosylation of target human cells, particularly as SARS-CoV-2 has the capacity to bind sialic acid which is a common, and highly variable, terminal modification of glycans. The viral spike glycoprotein (S) of SARS-CoV-2 and the human cellular receptor, angiotensin-converting enzyme 2 (ACE2) are both densely glycosylated. We therefore sought to investigate whether the glycosylation state of ACE2 impacts the interaction with SARS-CoV-2 viral spike. We generated a panel of engineered ACE2 glycoforms which were analyzed by mass spectrometry to reveal the site-specific glycan modifications. We then probed the impact of ACE2 glycosylation on S binding and revealed a subtle sensitivity with hypersialylated or oligomannose-type glycans slightly impeding the interaction. In contrast, deglycosylation of ACE2 did not influence SARS-CoV-2 binding. Overall, ACE2 glycosylation does not significantly influence viral spike binding. We suggest that any role of glycosylation in the pathobiology of SARS-CoV-2 will lie beyond its immediate impact of receptor glycosylation on virus binding. (C) 2020 The Author(s). Published by Elsevier Ltd.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据