ArticleJournal of the American Society for Mass Spectrometry2018
Comprehensive Proteoform Characterization of Plasma Complement Component C8αβγ by Hybrid Mass Spectrometry Approaches.
Article in Journal of the American Society for Mass Spectrometry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Glycosylation as an intricate post-translational modification process takes part in glycoproteins related immunity.Cell communication and signaling : CCS · 2025Review
- The ferroform and glycoform landscape of human milk lactoferrin dissected through hybrid mass spectrometric approaches.Frontiers in nutrition · 2025Article
- Article
- Charting the Proteoform Landscape of Serum Proteins in Individual Donors by High-Resolution Native Mass Spectrometry.Analytical chemistry · 2022Article
- Native Mass Spectrometry: Recent Progress and Remaining Challenges.Annual review of biophysics · 2022Review
- Characterizing Endogenous Protein Complexes with Biological Mass Spectrometry.Chemical reviews · 2022Review
- High-Resolution Native Mass Spectrometry.Chemical reviews · 2022Review
- Surface-Induced Dissociation for Protein Complex Characterization.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Review
- Comparative Analysis of Serum Proteins Between Hepatitis B Virus Genotypes B and C Infection by DIA-Based Quantitative Proteomics.Infection and drug resistance · 2021Article
- A wealth of genotype-specific proteoforms fine-tunes hemoglobin scavenging by haptoglobin.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Relating glycoprotein structural heterogeneity to function - insights from native mass spectrometry.Current opinion in structural biology · 2019Review
- Glycoproteogenomics: A Frequent Gene Polymorphism Affects the Glycosylation Pattern of the Human Serum Fetuin/α-2-HS-Glycoprotein.Molecular & cellular proteomics : MCP · 2019Article
- CryoEM reveals how the complement membrane attack complex ruptures lipid bilayers.Nature communications · 2018Article
- Similar Albeit Not the Same: In-Depth Analysis of Proteoforms of Human Serum, Bovine Serum, and Recombinant Human Fetuin.Journal of proteome research · 2018Article
- Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
The human complement hetero-trimeric C8αβγ (C8) protein assembly (~ 150 kDa) is an important component of the membrane attack complex (MAC). C8 initiates membrane penetration and coordinates MAC pore formation. Here, we charted in detail the structural micro-heterogeneity within C8, purified from human plasma, combining high-resolution native mass spectrometry and (glyco)peptide-centric proteomics. The intact C8 proteoform profile revealed at least ~ 20 co-occurring MS signals. Additionally, we employed ion exchange chromatography to separate purified C8 into four distinct fractions. Their native MS analysis revealed even more detailed structural micro-heterogeneity on C8. Subsequent peptide-centric analysis, by proteolytic digestion of C8 and LC-MS/MS, provided site-specific quantitative profiles of different types of C8 glycosylation. Combining all this data provides a detailed specification of co-occurring C8 proteoforms, including experimental evidence on N-glycosylation, C-mannosylation, and O-glycosylation. In addition to the known N-glycosylation sites, two more N-glycosylation sites were detected on C8. Additionally, we elucidated the stoichiometry of all C-mannosylation sites in all the thrombospondin-like (TSP) domains of C8α and C8β. Lastly, our data contain the first experimental evidence of O-linked glycans located on C8γ. Albeit low abundant, these O-glycans are the first PTMs ever detected on this subunit. By placing the observed PTMs in structural models of free C8 and C8 embedded in the MAC, it may be speculated that some of the newly identified modifications may play a role in the MAC formation. Graphical Abstract ᅟ.
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