ArticleThe Journal of biological chemistry2018
A potent complement factor C3-specific nanobody inhibiting multiple functions in the alternative pathway of human and murine complement.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed.
- The Promise of Single-Domain Antibodies as Ocular Therapeutics: A Narrative Review.International journal of molecular sciences · 2026Review
- Three cryo-EM structures of complement C3d-bound αScience advances · 2026Article
- Nanobody-based IgG simultaneously inhibit the allergenic and enzymatic activity of the dominant honeybee venom allergen.Nature communications · 2026Article
- Nanobody-based gene therapy targeting complement component C3 reduces choroidal neovascularization in mice.Molecular therapy. Methods & clinical development · 2025Article
- Proteolytic profiling of human plasma reveals an immunoactive complement C3 fragment.The EMBO journal · 2025Article
- Cryo-EM analysis of complement C3 reveals a reversible major opening of the macroglobulin ring.Nature structural & molecular biology · 2025Article
- Affinity-stability trade-off mechanism of residue 35 in framework region 2 of VProtein science : a publication of the Protein Society · 2025Article
- Acquired drivers of C3 glomerulopathy.Clinical kidney journal · 2025Review
- Reconstitution of the alternative pathway of the complement system enables rapid delineation of the mechanism of action of novel inhibitors.The Journal of biological chemistry · 2024Article
- Filtration and tubular handling of EWE-hC3Nb1, a complement inhibitor nanobody, in wild type mice and a mouse model of proteinuric kidney disease.FEBS open bio · 2024Article
- Modular design of bi- and multi-specific knob domain fusions.Frontiers in immunology · 2024Article
- Human Complement Inhibits Myophages againstViruses · 2023Article
- Novel homozygous CD46 variant with C-isoform expression affects C3b inactivation in atypical hemolytic uremic syndrome.European journal of immunology · 2022Article
- Structure determination of an unstable macromolecular complex enabled by nanobody-peptide bridging.Protein science : a publication of the Protein Society · 2022Article
- Multifaceted Activities of Seven Nanobodies against Complement C4b.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Structure-Guided Engineering of a Complement Component C3-Binding Nanobody Improves Specificity and Adds Cofactor Activity.Frontiers in immunology · 2022Article
- Complement component C3: A structural perspective and potential therapeutic implications.Seminars in immunology · 2022Review
- The human natural anti-αGal antibody targets common pathogens by broad-spectrum polyreactivity.Immunology · 2021Article
- Nanobodies Provide Insight into the Molecular Mechanisms of the Complement Cascade and Offer New Therapeutic Strategies.Biomolecules · 2021Review
- Analysis of complement deposition and processing on Chlamydia trachomatis.Medical microbiology and immunology · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The complement system is a complex, carefully regulated proteolytic cascade for which suppression of aberrant activation is of increasing clinical relevance, and inhibition of the complement alternative pathway is a subject of intense research. Here, we describe the nanobody hC3Nb1 that binds to multiple functional states of C3 with subnanomolar affinity. The nanobody causes a complete shutdown of alternative pathway activity in human and murine serum when present in concentrations comparable with that of C3, and hC3Nb1 is shown to prevent proconvertase assembly, as well as binding of the C3 substrate to C3 convertases. Our crystal structure of the C3b-hC3Nb1 complex and functional experiments demonstrate that proconvertase formation is blocked by steric hindrance between the nanobody and an Asn-linked glycan on complement factor B. In addition, hC3Nb1 is shown to prevent factor H binding to C3b, rationalizing its inhibition of factor I activity. Our results identify hC3Nb1 as a versatile, inexpensive, and powerful inhibitor of the alternative pathway in both human and murine
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.