ArticleMolecular & cellular proteomics : MCP2016
Structure of Complement C3(H2O) Revealed By Quantitative Cross-Linking/Mass Spectrometry And Modeling.
Article in Molecular & cellular proteomics : MCP, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 80 citations in OpenAlex.
- Advances in Complement Research: from Pathophysiology to Precision Medicine.Physiology (Bethesda, Md.) · 2026Review
- Complement-Mediated Kidney Diseases: Role of Alternative Pathway in Glomerular Inflammation.Kidney international reports · 2026Review
- Activation of the alternative complement pathway and its relevance for sodium retention in experimental nephrotic syndrome.Pflugers Archiv : European journal of physiology · 2026Article
- Structural insights into C3 convertase activity of the classical pathway of complement.Nature communications · 2025Article
- The Inhibitory Effects of a Factor B-Binding DNA Aptamer Family Supersede the Gain of Function of Factor B Variants Associated with Atypical Hemolytic Uremic Syndrome.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Roles of complement system in psychiatric disorders.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2023Article
- Cryo-EM structures of Trypanosoma brucei gambiense ISG65 with human complement C3 and C3b and their roles in alternative pathway restriction.Nature communications · 2023Article
- Alternative pathway activation: Ever ancient and ever new.Immunological reviews · 2023Review
- Structural modelling of human complement FHR1 and two of its synthetic derivatives provides insight into their in-vivo functions.Computational and structural biotechnology journal · 2023Article
- New system for archiving integrative structures.Acta crystallographica. Section D, Structural biology · 2021Article
- Targeting complement components C3 and C5 for the retina: Key concepts and lingering questions.Progress in retinal and eye research · 2021Review
- Interlink between Inflammation and Oxidative Stress in Age-Related Macular Degeneration: Role of Complement Factor H.Biomedicines · 2021Review
- Emerging Role of C5 Complement Pathway in Peripheral Neuropathies: Current Treatments and Future Perspectives.Biomedicines · 2021Review
- More than a Pore: Nonlytic Antimicrobial Functions of Complement and Bacterial Strategies for Evasion.Microbiology and molecular biology reviews : MMBR · 2021Review
- Complement in neurological disorders and emerging complement-targeted therapeutics.Nature reviews. Neurology · 2020Review
- Coarse-grained (hybrid) integrative modeling of biomolecular interactions.Computational and structural biotechnology journal · 2020Review
- Combining SPR with atomic-force microscopy enables single-molecule insights into activation and suppression of the complement cascade.The Journal of biological chemistry · 2019Article
- Federating Structural Models and Data: Outcomes from A Workshop on Archiving Integrative Structures.Structure (London, England : 1993) · 2019Article
- Article
- An integrated workflow for crosslinking mass spectrometry.Molecular systems biology · 2019Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 4 countries.
Funding
Abstract
The slow but spontaneous and ubiquitous formation of C3(H2O), the hydrolytic and conformationally rearranged product of C3, initiates antibody-independent activation of the complement system that is a key first line of antimicrobial defense. The structure of C3(H2O) has not been determined. Here we subjected C3(H2O) to quantitative cross-linking/mass spectrometry (QCLMS). This revealed details of the structural differences and similarities between C3(H2O) and C3, as well as between C3(H2O) and its pivotal proteolytic cleavage product, C3b, which shares functionally similarity with C3(H2O). Considered in combination with the crystal structures of C3 and C3b, the QCMLS data suggest that C3(H2O) generation is accompanied by the migration of the thioester-containing domain of C3 from one end of the molecule to the other. This creates a stable C3b-like platform able to bind the zymogen, factor B, or the regulator, factor H. Integration of available crystallographic and QCLMS data allowed the determination of a 3D model of the C3(H2O) domain architecture. The unique arrangement of domains thus observed in C3(H2O), which retains the anaphylatoxin domain (that is excised when C3 is enzymatically activated to C3b), can be used to rationalize observed differences between C3(H2O) and C3b in terms of complement activation and regulation.
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