A synthetic protein as efficient multitarget regulator against complement over-activation
Abstract: The complement system constitutes the innate defense against pathogens. Its dysregulation leads to diseases and is a critical determinant in many viral infections, e.g., COVID-19. Factor H (FH) is the main regulator of the alternative pathway of complement activation and could be a therapy to restore homeostasis. However, recombinant FH is not available. Engineered FH versions may be alternative therapeutics. Here, we designed a synthetic protein, MFHR13, as a multitarget complement regulator. It combines the dimerization and C5-regulatory domains of human FH-related protein 1 (FHR1) with the C3-regulatory and cell surface recognition domains of human FH, including SCR 13. In summary, the fusion protein MFHR13 comprises SCRs FHR11-2:FH1-4:FH13:FH19-20. It protects sheep erythrocytes from complement attack exhibiting 26 and 4-fold the regulatory activity of eculizumab and human FH, respectively. Furthermore, we demonstrate that MFHR13 and FHR1 bind to all proteins forming the membrane attack complex, which contributes to the mechanistic understanding of FHR1. We consider MFHR13 a promising candidate as therapeutic for complement-associated diseases
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Anmerkungen
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Communications biology. - 5 (2022) , 152, ISSN: 2399-3642
- Ereignis
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Veröffentlichung
- (wo)
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Freiburg
- (wer)
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Universität
- (wann)
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2022
- Urheber
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Ruiz-Molina, Natalia
Parsons, Juliana
Müller, Madeleine
Hoernstein, Sebastian
Bohlender, Lennard
Pumple, Steffen
Zipfel, Peter F.
Häffner, Karsten
Reski, Ralf
Decker, Eva
- DOI
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10.1038/s42003-022-03094-5
- URN
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urn:nbn:de:bsz:25-freidok-2253647
- Rechteinformation
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Kein Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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25.03.2025, 13:53 MEZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- Ruiz-Molina, Natalia
- Parsons, Juliana
- Müller, Madeleine
- Hoernstein, Sebastian
- Bohlender, Lennard
- Pumple, Steffen
- Zipfel, Peter F.
- Häffner, Karsten
- Reski, Ralf
- Decker, Eva
- Universität
Entstanden
- 2022
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