PuSH - Publikationsserver des Helmholtz Zentrums München

Svilenov, H.L.* ; Delhommel, F. ; Siebenmorgen, T. ; Rührnößl, F.* ; Popowicz, G.M. ; Reiter, A.* ; Sattler, M. ; Brockmeyer, C.* ; Buchner, J.*

Extrinsic stabilization of antiviral ACE2-Fc fusion proteins targeting SARS-CoV-2.

Comm. Biol. 6:386 (2023)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
Altmetric
Weitere Metriken?
[➜Einloggen]
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Angiotensin-converting Enzyme; Binding; Spike
ISSN (print) / ISBN 2399-3642
e-ISSN 2399-3642
Zeitschrift Communications Biology
Quellenangaben Band: 6, Heft: 1, Seiten: , Artikelnummer: 386 Supplement: ,
Verlag Springer
Verlagsort London
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Structural Biology (STB)
Förderungen DFG
Peter und Traudl Engelhorn Stiftung
Deutsche Forschungsgemeinschaft