ArticleThe American journal of pathology2005
Binding of complement factor H to endothelial cells is mediated by the carboxy-terminal glycosaminoglycan binding site.
Article in The American journal of pathology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 117 citations in OpenAlex.
- Therapeutic Targeting of the Complement System: From Rare Diseases to Pandemics.Pharmacological reviews · 2021Pooled it
- Trial
- Unraveling the Intricate Web: Complement Activation Shapes the Pathogenesis of Sepsis-Induced Coagulopathy.Journal of innate immunity · 2024Review
- The human factor H protein family - an update.Frontiers in immunology · 2024Review
- PepO and CppA modulateVirulence · 2023Article
- Molecular dynamics-based descriptors of 3-O-Sulfated Heparan sulfate as contributors of protein binding specificity.Computational biology and chemistry · 2022Article
- Exploratory Investigation of the Plasma Proteome Associated with the Endotheliopathy of Trauma.International journal of molecular sciences · 2022Article
- Atypical Hemolytic Uremic Syndrome-Associated FHR1 Isoform FHR1*B Enhances Complement Activation and Inflammation.Frontiers in immunology · 2022Article
- Complement Factor H Family Proteins Modulate Monocyte and Neutrophil Granulocyte Functions.Frontiers in immunology · 2021Article
- Article
- Potentiation of complement regulator factor H protects human endothelial cells from complement attack in aHUS sera.Blood advances · 2019Article
- The multifaceted role of complement in kidney transplantation.Nature reviews. Nephrology · 2018Review
- Genotype-phenotype correlations of low-frequency variants in the complement system in renal disease and age-related macular degeneration.Clinical genetics · 2018Article
- Dengue Virus Induces Increased Activity of the Complement Alternative Pathway in Infected Cells.Journal of virology · 2018Article
- Self-Damage Caused by Dysregulation of the Complement Alternative Pathway: Relevance of the Factor H Protein Family.Frontiers in immunology · 2018Review
- Matchout deuterium labelling of proteins for small-angle neutron scattering studies using prokaryotic and eukaryotic expression systems and high cell-density cultures.European biophysics journal : EBJ · 2017Article
- HUS and atypical HUS.Blood · 2017Review
- Article
- The Murine Factor H-Related Protein FHR-B Promotes Complement Activation.Frontiers in immunology · 2017Article
- Properdin: a tightly regulated critical inflammatory modulator.Immunological reviews · 2016Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Factor H (FH), the major fluid phase regulator of the alternative complement pathway, mediates protection of plasma-exposed host structures. It has recently been shown that short consensus repeats 19 to 20 of FH are mutational hot spots associated with atypical hemolytic uremic syndrome (aHUS), a disease with endothelial cell damage. Domain 20 of FH contains binding sites for heparin, C3b, and the cleavage product C3d. To study the role of these binding sites in target recognition, we performed site-directed mutagenesis in domain 20 and assayed the resulting recombinant proteins. The mutant FH15-20A (substitutions R1203E, R1206E, and R1210S) bound neither heparin nor endothelial cells. Similarly, an aHUS-derived mutant FH protein (E1172Stop, lacking domain 20) failed to bind endothelial cells and showed impaired binding to heparin. Binding of FH to endothelial cells was inhibited by heparin and a specific monoclonal antibody that inhibited heparin but not C3d binding, demonstrating that the heparin site on domains 19 to 20 mediates interaction of FH to endothelial cells. Binding of FH15-20 to heparin was inhibited by several cell surface- and basement membrane-associated glycosaminoglycans, suggesting that binding site specificity is not restricted to heparin. Thus, defective heparin/glycosaminoglycan-binding site on domains 19 to 20 of FH most probably mediates complement-induced endothelial cell damage in aHUS.
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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.