ArticleThe EMBO journal2016
Regulators of complement activity mediate inhibitory mechanisms through a common C3b-binding mode.
Article in The EMBO journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 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
79 citing papers in PubMed, 1 synthesis or guideline pooled it, 105 citations in OpenAlex.
- Therapeutic Targeting of the Complement System: From Rare Diseases to Pandemics.Pharmacological reviews · 2021Pooled it
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- CTx001 for Geographic Atrophy: A Gene Therapy Expressing Soluble, Truncated Complement Receptor 1 (Mini-CR1).Ophthalmology science · 2026Article
- Discovering nanoparticle corona ligands for liver macrophage capture.Nature nanotechnology · 2025Article
- The multiverse of CD46 and oncologic interactions.The Journal of clinical investigation · 2025Review
- A novel and rapid method to purify the human complement opsonin C3b from human plasma.Frontiers in immunology · 2025Article
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- Identification of mpox M1R and B6R monoclonal and bispecific antibodies that efficiently neutralize authentic mpox virus.Emerging microbes & infections · 2024Article
- CG001, a C3b-targeted complement inhibitor, blocks 3 complement pathways: development and preclinical evaluation.Blood advances · 2024Article
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- Triple-fusion protein (TriFu): A potent, targeted, enzyme-like inhibitor of all three complement activation pathways.The Journal of biological chemistry · 2024Article
- Inhibition of acute complement responses towards bolus-injected nanoparticles using targeted short-circulating regulatory proteins.Nature nanotechnology · 2024Article
- A guide to complement biology, pathology and therapeutic opportunity.Nature reviews. Immunology · 2024Review
- Complement-dependent uptake of nanoparticles by blood phagocytes: brief overview and perspective.Current opinion in biotechnology · 2024Review
- Voluntary wheel running prevents formation of membrane attack complexes and myelin degradation after peripheral nerve injury.Brain, behavior, and immunity · 2024Article
- The human factor H protein family - an update.Frontiers in immunology · 2024Review
- New Insights into the Complement Receptor of the Ig Superfamily Obtained from Structural and Functional Studies on Two Mutants.ImmunoHorizons · 2023Article
- The Molecular Mechanisms of Complement Receptor 1-It Is Complicated.Biomolecules · 2023Review
- Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Regulators of complement activation (RCA) inhibit complement-induced immune responses on healthy host tissues. We present crystal structures of human RCA (MCP, DAF, and CR1) and a smallpox virus homolog (SPICE) bound to complement component C3b. Our structural data reveal that up to four consecutive homologous CCP domains (i-iv), responsible for inhibition, bind in the same orientation and extended arrangement at a shared binding platform on C3b. Large sequence variations in CCP domains explain the diverse C3b-binding patterns, with limited or no contribution of some individual domains, while all regulators show extensive contacts with C3b for the domains at the third site. A variation of ~100° rotation around the longitudinal axis is observed for domains binding at the fourth site on C3b, without affecting the overall binding mode. The data suggest a common evolutionary origin for both inhibitory mechanisms, called decay acceleration and cofactor activity, with variable C3b binding through domains at sites ii, iii, and iv, and provide a framework for understanding RCA disease-related mutations and immune evasion.
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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.