Trial reportThe Journal of biological chemistry2013
Binding of complement inhibitor C4b-binding protein to a highly virulent Streptococcus pyogenes M1 strain is mediated by protein H and enhances adhesion to and invasion of endothelial cells.
Trial report in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Association of complement receptor 2 polymorphisms with innate resistance to HIV-1 infection.Genes and immunity · 2015Pooled it
- Molecular mechanism of complement interference by Streptococcus pyogenes nuclease A.Communications biology · 2026Article
- Host-response trajectories in necrotizing fasciitis: host-pathogen interactions, immune evasion, and immunoparalysis.Frontiers in cellular and infection microbiology · 2026Review
- Unveiling the impact ofInfection and immunity · 2024Article
- EmergentInfection and immunity · 2024Article
- Article
- C4b-Binding Protein and Factor H Attenuate NLRP3 Inflammasome-Mediated Signalling Response during Group A Streptococci Infection in Human Cells.Journal of innate immunity · 2024Article
- Diverse Functions of C4b-Binding Protein in Health and Disease.Journal of immunology (Baltimore, Md. : 1950) · 2023Review
- Edwardsiella tarda TraT is an anti-complement factor and a cellular infection promoter.Communications biology · 2022Article
- Age-associated changes in microglia and astrocytes ameliorate blood-brain barrier dysfunction.Molecular therapy. Nucleic acids · 2021Article
- NontypeableJournal of immunology (Baltimore, Md. : 1950) · 2021Article
- Complement Evasion Strategies of Human Pathogenic Bacteria.Indian journal of microbiology · 2020Review
- C4b Binding Protein Acts as an Innate Immune Effector Against Influenza A Virus.Frontiers in immunology · 2020Article
- Intracellular Invasion byMicrobiology spectrum · 2019Review
- Rapid determination of quaternary protein structures in complex biological samples.Nature communications · 2019Article
- The Molecular Basis of Human IgG-Mediated Enhancement of C4b-Binding Protein Recruitment to Group A Streptococcus.Frontiers in immunology · 2019Article
- Catch Me if You Can: Streptococcus pyogenes Complement Evasion Strategies.Journal of innate immunity · 2019Review
- Human IgG Increases Virulence ofJournal of immunology (Baltimore, Md. : 1950) · 2018Article
- Variation, Indispensability, and Masking in the M protein.Trends in microbiology · 2018Review
- Sickening or Healing the Heart? The Association of Ficolin-1 and Rheumatic Fever.Frontiers in immunology · 2018Observational
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Streptococcus pyogenes AP1, a strain of the highly virulent M1 serotype, uses exclusively protein H to bind the complement inhibitor C4b-binding protein (C4BP). We found a strong correlation between the ability of AP1 and its isogenic mutants lacking protein H to inhibit opsonization with complement C3b and binding of C4BP. C4BP bound to immobilized protein H or AP1 bacteria retained its cofactor activity for degradation of (125)I-C4b. Furthermore, C4b deposited from serum onto AP1 bacterial surfaces was processed into C4c/C4d fragments, which did not occur on strains unable to bind C4BP. Recombinant C4BP mutants, which (i) lack certain CCP domains or (ii) have mutations in single aa as well as (iii) mutants with additional aa between different CCP domains were used to determine that the binding is mainly mediated by a patch of positively charged amino acid residues at the interface of domains CCP1 and CCP2. Using recombinant protein H fragments, we narrowed down the binding site to the N-terminal domain A. With a peptide microarray, we identified one single 18-amino acid-long peptide comprising residues 92-109, which specifically bound C4BP. Biacore was used to determine KD = 6 × 10(-7) M between protein H and a single subunit of C4BP. C4BP binding also correlated with elevated levels of adhesion and invasion to endothelial cells. Taken together, we identified the molecular basis of C4BP-protein H interaction and found that it is not only important for decreased opsonization but also for invasion of endothelial cells by S. pyogenes.
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Registered trials
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.