ArticleMolecular immunology2008
Dynamic structural changes during complement C3 activation analyzed by hydrogen/deuterium exchange mass spectrometry.
Article in Molecular immunology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Therapeutic Targeting of the Complement System: From Rare Diseases to Pandemics.Pharmacological reviews · 2021Pooled it
- Elevated levels of nitrotyrosine-modified protein adducts and their association with the severity of primary sjogren's syndrome and secondary sjogren's syndrome with rheumatoid arthritis in Taiwanese Patients.Clinical rheumatology · 2026Article
- Cryo-EM analysis of complement C3 reveals a reversible major opening of the macroglobulin ring.Nature structural & molecular biology · 2025Article
- Generation of Novel Human Red Blood Cell-Bearing Humanized Mouse Models Based on C3-Deficient NOG Mice.Frontiers in immunology · 2021Article
- Development and Optimization of an ELISA to Quantitate C3(HFrontiers in immunology · 2019Article
- Revealing Unknown Protein Structures Using Computational Conformational Sampling Guided by Experimental Hydrogen-Exchange Data.International journal of molecular sciences · 2018Article
- Native State of Complement Protein C3d Analysed via Hydrogen Exchange and Conformational Sampling.International journal of computational biology and drug design · 2018Article
- Structural Implications for the Formation and Function of the Complement Effector Protein iC3b.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Rare loss-of-function mutation in complement component C3 provides insight into molecular and pathophysiological determinants of complement activity.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Molecular interaction between natural IgG and ficolin--mechanistic insights on adaptive-innate immune crosstalk.Scientific reports · 2014Article
- Progress and Trends in Complement Therapeutics.Advances in experimental medicine and biology · 2013Article
- Manipulating the mediator: modulation of the alternative complement pathway C3 convertase in health, disease and therapy.Immunobiology · 2012Review
- Advances in understanding the structure, function, and mechanism of the SCIN and Efb families of Staphylococcal immune evasion proteins.Advances in experimental medicine and biology · 2012Review
- Allosteric inhibition of complement function by a staphylococcal immune evasion protein.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Steroid and protein ligand binding to cytochrome P450 46A1 as assessed by hydrogen-deuterium exchange and mass spectrometry.Biochemistry · 2009Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Proteolytic cleavage of component C3 to C3b is a central step in the activation of complement. Whereas C3 is largely biologically inactive, C3b is directly involved in various complement activities. While the recently described crystal structures of C3 and C3b provide a molecular basis of complement activation, they do not reflect the dynamic changes that occur in solution. In addition, the available C3b structures diverge in some important aspects. Here we have utilized hydrogen/deuterium exchange coupled with mass spectrometry (HDX-MS) to investigate relative changes in the solution-phase structures of C3 and C3b. By combining two forms of mass spectrometry we could maximize the primary sequence coverage of C3b and demonstrate the feasibility of this method for large plasma proteins. While the majority of the 82 peptides that could be followed over time showed only minor alterations in HDX, we observed clear changes in solvent accessibility for 16 peptides, primarily in the alpha-chain (alpha'NT, MG6-8, CUB, TED, C345C domains). Most of these peptides could be directly linked to the structural transitions visible in the crystal structures and revealed additional information about the probability of the structural variants of C3b. In addition, a discontinuous cluster of seven peptides in the MG3, MG6, LNK and alpha'NT domains showed a decreased accessibility after activation to C3b. Although no gross conformational changes are detected in the crystal structure, this area may reflect a structurally flexible region in solution that contributes to C3 activation and function.
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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.