ArticleJournal of molecular biology2012
Solution structure of CCP modules 10-12 illuminates functional architecture of the complement regulator, factor H.
Article in Journal of molecular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 24 citations in OpenAlex.
- AnFrontiers in immunology · 2023Article
- An Evaluation of the Complement-Regulating Activities of Human Complement Factor H (FH) Variants Associated With Age-Related Macular Degeneration.Investigative ophthalmology & visual science · 2022Article
- The solution structure of the complement deregulator FHR5 reveals a compact dimer and provides new insights into CFHR5 nephropathy.The Journal of biological chemistry · 2020Article
- Combining SPR with atomic-force microscopy enables single-molecule insights into activation and suppression of the complement cascade.The Journal of biological chemistry · 2019Article
- Potentiation of complement regulator factor H protects human endothelial cells from complement attack in aHUS sera.Blood advances · 2019Article
- 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
- Biophysical analysis of sialic acid recognition by the complement regulator Factor H.Glycobiology · 2018Article
- An Engineered Complement Factor H Construct for Treatment of C3 Glomerulopathy.Journal of the American Society of Nephrology : JASN · 2018Article
- Article
- Complement factor H in host defense and immune evasion.Cellular and molecular life sciences : CMLS · 2017Review
- Protection of host cells by complement regulators.Immunological reviews · 2016Review
- Complement receptor activity of recombinant porcine CR1-like protein expressed in a eukaryotic system.Immunologic research · 2016Article
- Comparative Analysis of Novel Complement-Targeted Inhibitors, MiniFH, and the Natural Regulators Factor H and Factor H-like Protein 1 Reveal Functional Determinants of Complement Regulation.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Complement System Part I - Molecular Mechanisms of Activation and Regulation.Frontiers in immunology · 2015Review
- New functional and structural insights from updated mutational databases for complement factor H, Factor I, membrane cofactor protein and C3.Bioscience reports · 2014Article
- American Society of Nephrology clinical pathological conference.Clinical journal of the American Society of Nephrology : CJASN · 2014Article
- Decoding the components of dynamics in three-domain proteins.Journal of computational chemistry · 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
- Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
The 155-kDa plasma glycoprotein factor H (FH), which consists of 20 complement control protein (CCP) modules, protects self-tissue but not foreign organisms from damage by the complement cascade. Protection is achieved by selective engagement of FH, via CCPs 1-4, CCPs 6-8 and CCPs 19-20, with polyanion-rich host surfaces that bear covalently attached, activation-specific, fragments of complement component C3. The role of intervening CCPs 9-18 in this process is obscured by lack of structural knowledge. We have concatenated new high-resolution solution structures of overlapping recombinant CCP pairs, 10-11 and 11-12, to form a three-dimensional structure of CCPs 10-12 and validated it by small-angle X-ray scattering of the recombinant triple-module fragment. Superimposing CCP 12 of this 10-12 structure with CCP 12 from the previously solved CCP 12-13 structure yielded an S-shaped structure for CCPs 10-13 in which modules are tilted by 80-110° with respect to immediate neighbors, but the bend between CCPs 10 and 11 is counter to the arc traced by CCPs 11-13. Including this four-CCP structure in interpretation of scattering data for the longer recombinant segments, CCPs 10-15 and 8-15, implied flexible attachment of CCPs 8 and 9 to CCP 10 but compact and intimate arrangements of CCP 14 with CCPs 12, 13 and 15. Taken together with difficulties in recombinant production of module pairs 13-14 and 14-15, the aberrant structure of CCP 13 and the variability of 13-14 linker sequences among orthologues, a structural dependency of CCP 14 on its neighbors is suggested; this has implications for the FH mechanism.
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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.