Extrinsic stabilization of antiviral ACE2-Fc fusion proteins targeting SARS-CoV-2.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
08 04 2023
08 04 2023
Historique:
received:
14
12
2022
accepted:
24
03
2023
medline:
11
4
2023
entrez:
8
4
2023
pubmed:
9
4
2023
Statut:
epublish
Résumé
The angiotensin-converting enzyme 2 (ACE2) is a viral receptor used by sarbecoviruses to infect cells. Fusion proteins comprising extracellular ACE2 domains and the Fc part of immunoglobulins exhibit high virus neutralization efficiency, but the structure and stability of these molecules are poorly understood. We show that although the hinge between the ACE2 and the IgG4-Fc is highly flexible, the conformational dynamics of the two ACE2 domains is restricted by their association. Interestingly, the conformational stability of the ACE2 moiety is much lower than that of the Fc part. We found that chemical compounds binding to ACE2, such as DX600 and MLN4760, can be used to strongly increase the thermal stability of the ACE2 by different mechanisms. Together, our findings reveal a general concept for stabilizing the labile receptor segments of therapeutic antiviral fusion proteins by chemical compounds.
Identifiants
pubmed: 37031320
doi: 10.1038/s42003-023-04762-w
pii: 10.1038/s42003-023-04762-w
pmc: PMC10082628
doi:
Substances chimiques
Antiviral Agents
0
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
386Informations de copyright
© 2023. The Author(s).
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