Subtle Influence of ACE2 Glycan Processing on SARS-CoV-2 Recognition

JOURNAL OF MOLECULAR BIOLOGY

卷:433

Article

Allen, Joel D.¹  Watanabe, Yasunori^1,2,3  Chawla, Himanshi¹  Newby, Maddy L.¹  Crispin, Max¹ 

[1] Univ Southampton, Sch Biol Sci, Southampton SO17 1BJ, Hants, England

[2] Univ Oxford, Oxford Glycobiol Inst, Dept Biochem, South Parks Rd, Oxford OX1 3QU, England

[3] Univ Oxford, Wellcome Ctr Human Genet, Div Struct Biol, Oxford OX3 7BN, England

关键词: SARS-CoV-2;    ACE2;    glycosylation;    surface plasmon resonance;    glycan engineering;   

DOI  :  10.1016/j.jmb.2020.166762

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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