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Engineering (Beijing) . Mass Spectrometry Analysis of Newly Emerging Coronavirus HCoV-19 Spike Protein and Human ACE2 Reveals Camouflaging Glycans

tetano

Editor, Senior Moderator
Engineering (Beijing)


. 2020 Aug 30.
doi: 10.1016/j.eng.2020.07.014. Online ahead of print.
Mass Spectrometry Analysis of Newly Emerging Coronavirus HCoV-19 Spike Protein and Human ACE2 Reveals Camouflaging Glycans and Unique Post-Translational Modifications


Zeyu Sun[SUP] 1 [/SUP], Keyi Ren[SUP] 1 [/SUP], Xing Zhang[SUP] 2 [/SUP], Jinghua Chen[SUP] 2 [/SUP], Zhengyi Jiang[SUP] 1 [/SUP], Jing Jiang[SUP] 1 [/SUP], Feiyang Ji[SUP] 1 [/SUP], Xiaoxi Ouyang[SUP] 1 [/SUP], Lanjuan Li[SUP] 1 [/SUP]



Affiliations

Abstract

The COVID-19 pandemic has led to worldwide efforts to understand the biological traits of the newly identified HCoV-19 virus. In this mass spectrometry (MS)-based study, we reveal that out of 21 possible glycosites in the HCoV-19 S protein, 20 are completely occupied by N-glycans, predominantly of the oligomannose type. All seven glycosylation sites in human angiotensin I converting enzyme 2 (hACE2) were found to be completely occupied, mainly by complex N-glycans. However, glycosylation did not directly contribute to the binding affinity between HCoV-19 S and hACE2. Additional post-translational modification (PTM) was identified, including multiple methylated sites in both proteins and multiple sites with hydroxylproline in hACE2. Refined structural models of HCoV-19 S and hACE2 were built by adding N-glycan and PTMs to recently published cryogenic electron microscopy (cryo-EM) structures. The PTM and glycan maps of HCoV-19 S and hACE2 provide additional structural details for studying the mechanisms underlying host attachment and the immune response of HCoV-19, as well as knowledge for developing desperately needed remedies and vaccines.

Keywords: COVID-19; N-glycosylation; Spike protein; Structure; hACE2.
 
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