Virus-Receptor Interactions of Glycosylated SARS-CoV-2 Spike and Human ACE2 Receptor
Virus-Receptor Interactions of Glycosylated SARS-CoV-2 Spike and Human ACE2 Receptor
SUMMARY The current COVID-19 pandemic is caused by the SARS-CoV-2 betacoronavirus, which utilizes its highly glycosylated trimeric Spike protein to bind to the cell surface receptor ACE2 glycoprotein and facilitate host cell entry. We utilized glycomics-informed glycoproteomics to characterize site-specific microheterogeneity of glycosylation for a recombinant trimer spike mimetic immunogen and for a soluble version of human ACE2. We combined this information with bioinformatic analyses of natural variants and with existing 3D-structures of both glycoproteins to generate molecular dynamic simulations of each glycoprotein alone and interacting with one another. Our results highlight roles for glycans in sterically masking polypeptide epitopes and directly modulating Spike-ACE2 interactions. Furthermore, our results illustrate the impact of viral evolution and divergence on Spike glycosylation, as well as the influence of natural variants on ACE2 receptor glycosylation that, taken together, can facilitate immunogen design to achieve antibody neutralization and inform therapeutic strategies to inhibit viral infection.
Kellman Benjamin P.、Lewis Nathan E.、Chen Bing、Wells Lance、Grant Oliver C.、Aoki Kazuhiro、Bridger Robert、Zhao Peng、Rosenbalm Katelyn E.、Tiemeyer Michael、Brindley Melinda A.、Xiao Tianshu、Praissman Jeremy L.、Cai Yongfei、Woods Robert J.、Barouch Dan H.
Departments of Pediatrics and Bioengineering, University of CaliforniaDepartments of Pediatrics and Bioengineering, University of California||Novo Nordisk Foundation Center for Biosustainability at UC San DiegoDivision of Molecular Medicine, Children?ˉs Hospital and Department of Pediatrics, Harvard Medical SchoolComplex Carbohydrate Research Center, Department of Biochemistry and Molecular Biology, and Department of Chemistry, University of GeorgiaComplex Carbohydrate Research Center, Department of Biochemistry and Molecular Biology, and Department of Chemistry, University of GeorgiaComplex Carbohydrate Research Center, Department of Biochemistry and Molecular Biology, and Department of Chemistry, University of GeorgiaComplex Carbohydrate Research Center, Department of Biochemistry and Molecular Biology, and Department of Chemistry, University of GeorgiaComplex Carbohydrate Research Center, Department of Biochemistry and Molecular Biology, and Department of Chemistry, University of GeorgiaComplex Carbohydrate Research Center, Department of Biochemistry and Molecular Biology, and Department of Chemistry, University of GeorgiaComplex Carbohydrate Research Center, Department of Biochemistry and Molecular Biology, and Department of Chemistry, University of GeorgiaDepartment of Infectious Diseases, Department of Population Health, Center for Vaccines and Immunology, College of Veterinary Medicine, University of GeorgiaDivision of Molecular Medicine, Children?ˉs Hospital and Department of Pediatrics, Harvard Medical SchoolComplex Carbohydrate Research Center, Department of Biochemistry and Molecular Biology, and Department of Chemistry, University of GeorgiaDivision of Molecular Medicine, Children?ˉs Hospital and Department of Pediatrics, Harvard Medical SchoolComplex Carbohydrate Research Center, Department of Biochemistry and Molecular Biology, and Department of Chemistry, University of GeorgiaCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School
基础医学生物科学研究方法、生物科学研究技术分子生物学
SARS-CoV-2COVID-19spike proteincoronavirusACE2glycoproteinglycosylationmass spectrometrymolecular dynamics3D-modeling
Kellman Benjamin P.,Lewis Nathan E.,Chen Bing,Wells Lance,Grant Oliver C.,Aoki Kazuhiro,Bridger Robert,Zhao Peng,Rosenbalm Katelyn E.,Tiemeyer Michael,Brindley Melinda A.,Xiao Tianshu,Praissman Jeremy L.,Cai Yongfei,Woods Robert J.,Barouch Dan H..Virus-Receptor Interactions of Glycosylated SARS-CoV-2 Spike and Human ACE2 Receptor[EB/OL].(2025-03-28)[2025-05-12].https://www.biorxiv.org/content/10.1101/2020.06.25.172403.点此复制
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