Mass Spectrometry Analysis of Newly Emerging Coronavirus HCoV-19 Spike Protein and Human ACE2 Reveals Camouflaging Glycans and Unique Post-Translational Modifications
The coronavirus disease 2019 (COVID-19) pandemic has led to worldwide efforts to understand the biological traits of the newly identified human coronavirus (HCoV-19) virus. In this mass spectrometry (MS)-based study, we reveal that out of 21 possible glycosites in the HCoV-19 spike protein (S protei...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-10-01
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| Series: | Engineering |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2095809920302344 |
| _version_ | 1829488657892900864 |
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| author | Zeyu Sun Keyi Ren Xing Zhang Jinghua Chen Zhengyi Jiang Jing Jiang Feiyang Ji Xiaoxi Ouyang Lanjuan Li |
| author_facet | Zeyu Sun Keyi Ren Xing Zhang Jinghua Chen Zhengyi Jiang Jing Jiang Feiyang Ji Xiaoxi Ouyang Lanjuan Li |
| author_sort | Zeyu Sun |
| collection | DOAJ |
| description | The coronavirus disease 2019 (COVID-19) pandemic has led to worldwide efforts to understand the biological traits of the newly identified human coronavirus (HCoV-19) virus. In this mass spectrometry (MS)-based study, we reveal that out of 21 possible glycosites in the HCoV-19 spike protein (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 protein 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 protein and hACE2 were built by adding N-glycan and PTMs to recently published cryogenic electron microscopy structures. The PTM and glycan maps of HCoV-19 S protein 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. |
| first_indexed | 2024-12-14T23:55:14Z |
| format | Article |
| id | doaj.art-ae387eb4ae9f40bd81cb198e0d8e9fa6 |
| institution | Directory Open Access Journal |
| issn | 2095-8099 |
| language | English |
| last_indexed | 2024-12-14T23:55:14Z |
| publishDate | 2021-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Engineering |
| spelling | doaj.art-ae387eb4ae9f40bd81cb198e0d8e9fa62022-12-21T22:43:09ZengElsevierEngineering2095-80992021-10-0171014411451Mass Spectrometry Analysis of Newly Emerging Coronavirus HCoV-19 Spike Protein and Human ACE2 Reveals Camouflaging Glycans and Unique Post-Translational ModificationsZeyu Sun0Keyi Ren1Xing Zhang2Jinghua Chen3Zhengyi Jiang4Jing Jiang5Feiyang Ji6Xiaoxi Ouyang7Lanjuan Li8State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310011, ChinaState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310011, ChinaDepartment of Biophysics & Center of Cryo-Electron Microscopy, School of Medicine, Zhejiang University, Hangzhou 310011, ChinaDepartment of Biophysics & Center of Cryo-Electron Microscopy, School of Medicine, Zhejiang University, Hangzhou 310011, ChinaState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310011, ChinaState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310011, ChinaState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310011, ChinaState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310011, ChinaState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310011, China; Corresponding author.The coronavirus disease 2019 (COVID-19) pandemic has led to worldwide efforts to understand the biological traits of the newly identified human coronavirus (HCoV-19) virus. In this mass spectrometry (MS)-based study, we reveal that out of 21 possible glycosites in the HCoV-19 spike protein (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 protein 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 protein and hACE2 were built by adding N-glycan and PTMs to recently published cryogenic electron microscopy structures. The PTM and glycan maps of HCoV-19 S protein 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.http://www.sciencedirect.com/science/article/pii/S2095809920302344N-glycosylationCOVID-19Spike proteinhACE2Structure |
| spellingShingle | Zeyu Sun Keyi Ren Xing Zhang Jinghua Chen Zhengyi Jiang Jing Jiang Feiyang Ji Xiaoxi Ouyang Lanjuan Li Mass Spectrometry Analysis of Newly Emerging Coronavirus HCoV-19 Spike Protein and Human ACE2 Reveals Camouflaging Glycans and Unique Post-Translational Modifications Engineering N-glycosylation COVID-19 Spike protein hACE2 Structure |
| title | Mass Spectrometry Analysis of Newly Emerging Coronavirus HCoV-19 Spike Protein and Human ACE2 Reveals Camouflaging Glycans and Unique Post-Translational Modifications |
| title_full | Mass Spectrometry Analysis of Newly Emerging Coronavirus HCoV-19 Spike Protein and Human ACE2 Reveals Camouflaging Glycans and Unique Post-Translational Modifications |
| title_fullStr | Mass Spectrometry Analysis of Newly Emerging Coronavirus HCoV-19 Spike Protein and Human ACE2 Reveals Camouflaging Glycans and Unique Post-Translational Modifications |
| title_full_unstemmed | Mass Spectrometry Analysis of Newly Emerging Coronavirus HCoV-19 Spike Protein and Human ACE2 Reveals Camouflaging Glycans and Unique Post-Translational Modifications |
| title_short | Mass Spectrometry Analysis of Newly Emerging Coronavirus HCoV-19 Spike Protein and Human ACE2 Reveals Camouflaging Glycans and Unique Post-Translational Modifications |
| title_sort | mass spectrometry analysis of newly emerging coronavirus hcov 19 spike protein and human ace2 reveals camouflaging glycans and unique post translational modifications |
| topic | N-glycosylation COVID-19 Spike protein hACE2 Structure |
| url | http://www.sciencedirect.com/science/article/pii/S2095809920302344 |
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