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

Mehdipour, A. R., & Hummer, G. (2021). Dual nature of human ACE2 glycosylation in binding to SARS-CoV-2 spike. Proceedings of the National Academy of Sciences of the United States of America, 118(19): e2100425118. doi:10.1073/pnas.2100425118.

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Genre: Journal Article

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 Creators:
Mehdipour, Ahmad Reza1, Author              
Hummer, Gerhard1, 2, Author              
Affiliations:
1Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Max Planck Society, ou_2068292              
2Institute for Biophysics, Goethe University Frankfurt, Frankfurt, Germany, ou_persistent22              

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Free keywords: ACE2 receptor, glycosylation, molecular dynamics, SARS-CoV-2, virus-host interaction
 Abstract: 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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Language(s): eng - English
 Dates: 2021-01-152021-03-122021-04-262021-05-11
 Publication Status: Published in print
 Pages: 8
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1073/pnas.2100425118
BibTex Citekey: mehdipour_dual_2021
 Degree: -

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Title: Proceedings of the National Academy of Sciences of the United States of America
  Other : PNAS
  Other : Proceedings of the National Academy of Sciences of the USA
  Abbreviation : Proc. Natl. Acad. Sci. U. S. A.
Source Genre: Journal
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Publ. Info: Washington, D.C. : National Academy of Sciences
Pages: - Volume / Issue: 118 (19) Sequence Number: e2100425118 Start / End Page: - Identifier: ISSN: 0027-8424
CoNE: https://pure.mpg.de/cone/journals/resource/954925427230