Dual nature of human ACE2 glycosylation in binding to SARS-CoV-2 spike

  • Binding of the spike protein of SARS-CoV-2 to the human angiotensin-converting enzyme 2 (ACE2) receptor triggers translocation of the virus into cells. Both the ACE2 receptor and the spike protein are heavily glycosylated, including at sites near their binding interface. We built fully glycosylated models of the ACE2 receptor bound to the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Using atomistic molecular dynamics (MD) simulations, we found that the glycosylation of the human ACE2 receptor contributes substantially to the binding of the virus. Interestingly, the glycans at two glycosylation sites, N90 and N322, have opposite effects on spike protein binding. The glycan at the N90 site partly covers the binding interface of the spike RBD. Therefore, this glycan can interfere with the binding of the spike protein and protect against docking of the virus to the cell. By contrast, the glycan at the N322 site interacts tightly with the RBD of the ACE2-bound spike protein and strengthens the complex. Remarkably, the N322 glycan binds to a conserved region of the spike protein identified previously as a cryptic epitope for a neutralizing antibody. By mapping the glycan binding sites, our MD simulations aid in the targeted development of neutralizing antibodies and SARS-CoV-2 fusion inhibitors.

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Metadaten
Author:Ahmad Reza MehdipourORCiD, Gerhard HummerORCiD
URN:urn:nbn:de:hebis:30:3-732877
DOI:https://doi.org/10.1073/pnas.2100425118
Parent Title (English):Proceedings of the National Academy of Sciences of the United States of America
Publisher:National Academy of Sciences
Place of publication:Washington, DC
Document Type:Article
Language:English
Date of Publication (online):2021/04/26
Date of first Publication:2021/04/26
Publishing Institution:Universit├Ątsbibliothek Johann Christian Senckenberg
Release Date:2023/03/24
Volume:118
Issue:19 e2100425118
Page Number:8
HeBIS-PPN:508619076
Institutes:Physik
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universit├Ątspublikationen
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International