Your browser doesn't support javascript.
loading
A Complement C3-Specific Nanobody for Modulation of the Alternative Cascade Identifies the C-Terminal Domain of C3b as Functional in C5 Convertase Activity.
Pedersen, Henrik; Jensen, Rasmus K; Jensen, Jens Magnus B; Fox, Rachel; Pedersen, Dennis V; Olesen, Heidi G; Hansen, Annette G; Christiansen, Dorte; Mazarakis, Sofia M M; Lojek, Neal; Hansen, Pernille; Gadeberg, Trine A F; Zarantonello, Alessandra; Laursen, Nick S; Mollnes, Tom Eirik; Johnson, Matthew B; Stevens, Beth; Thiel, Steffen; Andersen, Gregers R.
Afiliación
  • Pedersen H; Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus, Denmark.
  • Jensen RK; Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus, Denmark.
  • Jensen JMB; Department of Clinical Immunology, DK-8200 Skejby, Denmark.
  • Fox R; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142.
  • Pedersen DV; Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus, Denmark.
  • Olesen HG; Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus, Denmark.
  • Hansen AG; Department of Biomedicine, Aarhus University, DK-8000 Aarhus, Denmark.
  • Christiansen D; Research Laboratory, Nordland Hospital, 8092 Bodø, Norway.
  • Mazarakis SMM; Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus, Denmark.
  • Lojek N; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142.
  • Hansen P; Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus, Denmark.
  • Gadeberg TAF; Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus, Denmark.
  • Zarantonello A; Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus, Denmark.
  • Laursen NS; Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus, Denmark.
  • Mollnes TE; Research Laboratory, Nordland Hospital, 8092 Bodø, Norway.
  • Johnson MB; K.G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, 9037 Tromsø, Norway.
  • Stevens B; Department of Immunology, Oslo University Hospital, University of Oslo, 0318 Oslo, Norway.
  • Thiel S; Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, 7491 Trondheim, Norway; and.
  • Andersen GR; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142.
J Immunol ; 205(8): 2287-2300, 2020 10 15.
Article en En | MEDLINE | ID: mdl-32938727
The complement system is an intricate cascade of the innate immune system and plays a key role in microbial defense, inflammation, organ development, and tissue regeneration. There is increasing interest in developing complement regulatory and inhibitory agents to treat complement dysfunction. In this study, we describe the nanobody hC3Nb3, which is specific for the C-terminal C345c domain of human and mouse complement component C3/C3b/C3c and potently inhibits C3 cleavage by the alternative pathway. A high-resolution structure of the hC3Nb3-C345c complex explains how the nanobody blocks proconvertase assembly. Surprisingly, although the nanobody does not affect classical pathway-mediated C3 cleavage, hC3Nb3 inhibits classical pathway-driven hemolysis, suggesting that the C-terminal domain of C3b has an important function in classical pathway C5 convertase activity. The hC3Nb3 nanobody binds C3 with low nanomolar affinity in an SDS-resistant complex, and the nanobody is demonstrated to be a powerful reagent for C3 detection in immunohistochemistry and flow cytometry. Overall, the hC3Nb3 nanobody represents a potent inhibitor of both the alternative pathway and the terminal pathway, with possible applications in complement research, diagnostics, and therapeutics.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Complemento C3b / Vía Alternativa del Complemento / C5 Convertasa de la Vía Alternativa del Complemento / Anticuerpos de Dominio Único Límite: Animals / Humans Idioma: En Revista: J Immunol Año: 2020 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Complemento C3b / Vía Alternativa del Complemento / C5 Convertasa de la Vía Alternativa del Complemento / Anticuerpos de Dominio Único Límite: Animals / Humans Idioma: En Revista: J Immunol Año: 2020 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Estados Unidos