ArticleThe Journal of biological chemistry2008
Structure of the N-terminal region of complement factor H and conformational implications of disease-linked sequence variations.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 62 citations in OpenAlex.
- Common and rare variants in complement genes as biomarkers of COVID-19 infection and severity. A lesson to learn for emerging pathogens.Frontiers in immunology · 2026Article
- A novel and rapid method to purify the human complement opsonin C3b from human plasma.Frontiers in immunology · 2025Article
- The hypothetical molecular mechanism of the ethnic variations in the manifestation of age-related macular degeneration; focuses on the functions of the most significant susceptibility genes.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2024Review
- Polygenic Risk Score Impact on Susceptibility to Age-Related Macular Degeneration in Polish Patients.Journal of clinical medicine · 2022Article
- A synthetic protein as efficient multitarget regulator against complement over-activation.Communications biology · 2022Article
- Streptococcus Pneumoniae-Associated Hemolytic Uremic Syndrome in the Era of Pneumococcal Vaccine.Pathogens (Basel, Switzerland) · 2021Review
- Functional Characterization of Rare Genetic Variants in the N-Terminus of Complement Factor H in aHUS, C3G, and AMD.Frontiers in immunology · 2020Article
- Two distinct conformations of factor H regulate discrete complement-binding functions in the fluid phase and at cell surfaces.The Journal of biological chemistry · 2018Article
- Disease-linked mutations in factor H reveal pivotal role of cofactor activity in self-surface-selective regulation of complement activation.The Journal of biological chemistry · 2017Article
- Regulator-dependent mechanisms of C3b processing by factor I allow differentiation of immune responses.Nature structural & molecular biology · 2017Article
- Article
- Membrane-proximal TRAIL species are incapable of inducing short circuit apoptosis signaling: Implications for drug development and basic cytokine biology.Scientific reports · 2016Article
- Mutational analysis of Kaposica reveals that bridging of MG2 and CUB domains of target protein is crucial for the cofactor activity of RCA proteins.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Characterization of a factor H mutation that perturbs the alternative pathway of complement in a family with membranoproliferative GN.Journal of the American Society of Nephrology : JASN · 2014Article
- Using mutagenesis and structural biology to map the binding site for the Plasmodium falciparum merozoite protein PfRh4 on the human immune adherence receptor.The Journal of biological chemistry · 2014Article
- Atypical haemolytic-uraemic syndrome due to heterozygous mutations of CFH/CFHR1-3 and complement factor H 479.Blood transfusion = Trasfusione del sangue · 2014Article
- Atypical hemolytic uremic syndrome.Seminars in nephrology · 2013Review
- Solution structure of CCP modules 10-12 illuminates functional architecture of the complement regulator, factor H.Journal of molecular biology · 2012Article
- Use of time-resolved FRET to validate crystal structure of complement regulatory complex between C3b and factor H (N terminus).Protein science : a publication of the Protein Society · 2011Article
- Estimation of interdomain flexibility of N-terminus of factor H using residual dipolar couplings.Biochemistry · 2011Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Factor H is a regulatory glycoprotein of the complement system. We expressed the three N-terminal complement control protein modules of human factor H (FH1-3) and confirmed FH1-3 to be the minimal unit with cofactor activity for C3b proteolysis by factor I. We reconstructed FH1-3 from NMR-derived structures of FH1-2 and FH2-3 revealing an approximately 105-A-long rod-like arrangement of the modules. In structural comparisons with other C3b-engaging proteins, factor H module 3 most closely resembles factor B module 3, consistent with factor H competing with factor B for binding C3b. Factor H modules 1, 2, and 3 each has a similar backbone structure to first, second, and third modules, respectively, of functional sites in decay accelerating factor and complement receptor type 1; the equivalent intermodular tilt and twist angles are also broadly similar. Resemblance between molecular surfaces is closest for first modules but absent in the case of second modules. Substitution of buried Val-62 with Ile (a factor H single nucleotide polymorphism potentially protective for age-related macular degeneration and dense deposit disease) causes rearrangements within the module 1 core and increases thermal stability but does not disturb the interface with module 2. Replacement of partially exposed (in module 1) Arg-53 by His (an atypical hemolytic uremic syndrome-linked mutation) did not impair structural integrity at 37 degrees C, but this FH1-2 mutant was less stable at higher temperatures; furthermore, chemical shift differences indicated potential for small structural changes at the module 1-2 interface.
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