Evidence map›Paper›PMID 29532326›Full record

ArticleJournal of the American Society for Mass Spectrometry2018

Comprehensive Proteoform Characterization of Plasma Complement Component C8αβγ by Hybrid Mass Spectrometry Approaches.

Vojtech Franc, Jing Zhu, Albert J R Heck

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed.

  1. Review
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  8. Surface-Induced Dissociation for Protein Complex Characterization.Methods in molecular biology (Clifton, N.J.) · 2022
    Article
  9. Review
  10. Article
  11. 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 · 2020
    Article
  12. Review
  13. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors.

Vojtech FrancBiomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Padualaan 8, 3584 CH, Utrecht, The Netherlands.
Jing ZhuBiomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Padualaan 8, 3584 CH, Utrecht, The Netherlands.
Albert J R HeckBiomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Padualaan 8, 3584 CH, Utrecht, The Netherlands. a.j.r.heck@uu.nl.

Funding

Horizon 2020 686547Horizon 2020 Framework Programme 668036Nederlandse Organisatie voor Wetenschappelijk Onderzoek 184.032.201Nederlandse Organisatie voor Wetenschappelijk Onderzoek 718.015.003
6 · The paper itself

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.

Indexed as

Amino Acid SequenceChromatography, Ion ExchangeComplement C8GlycosylationHumansModels, MolecularPeptidesProtein MultimerizationTandem Mass SpectrometryComplement C8PeptidesC-glycosylationComplement component C8Glycopeptide-centric proteomicsGlycosylationIon-exchange chromatographyMembrane attack complexNative mass spectrometryN-glycosylationO-glycosylationPlasma proteins

Identifiers

PMID29532326
PMCPMC6003997

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Registered trials

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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.