Evidence map›Paper›PMID 33273015›Full record

ArticleThe Journal of biological chemistry

Hyper-truncated Asn355- and Asn391-glycans modulate the activity of neutrophil granule myeloperoxidase.

Harry C Tjondro, Julian Ugonotti, Rebeca Kawahara, Sayantani Chatterjee, Ian Loke, Siyun Chen, Fabian Soltermann, Hannes Hinneburg, Benjamin L Parker, Vignesh Venkatakrishnan and 8 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.8field-weighted citation impact, top 8% of its field
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

22 citing papers in PubMed, 41 citations in OpenAlex.

  1. Article
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  6. Glycoproteome remodeling and organelle-specificProceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  7. Caught red handed: modeling and confirmation of the myeloperoxidase ceruloplasmin alpha-thrombin complex.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2022
    Article
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  17. Review
  18. The Hitchhiker's guide to glycoproteomics.Biochemical Society transactions · 2021
    Review
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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

18 authors at 7 institutions in 5 countries.

Harry C TjondroDepartment of Molecular Sciences, Macquarie University, Sydney, New South Wales, Australia; Biomolecular Discovery Research Centre, Macquarie University, Sydney, New South Wales, Australia.
Julian UgonottiDepartment of Molecular Sciences, Macquarie University, Sydney, New South Wales, Australia; Biomolecular Discovery Research Centre, Macquarie University, Sydney, New South Wales, Australia.
Rebeca KawaharaDepartment of Molecular Sciences, Macquarie University, Sydney, New South Wales, Australia; Biomolecular Discovery Research Centre, Macquarie University, Sydney, New South Wales, Australia.
Sayantani ChatterjeeDepartment of Molecular Sciences, Macquarie University, Sydney, New South Wales, Australia; Biomolecular Discovery Research Centre, Macquarie University, Sydney, New South Wales, Australia.
Ian LokeCordlife Group Limited, Singapore, Singapore.
Siyun ChenDepartment of Chemistry, University of Oxford, Oxford, United Kingdom.
Fabian SoltermannDepartment of Chemistry, University of Oxford, Oxford, United Kingdom.
Hannes HinneburgDepartment of Molecular Sciences, Macquarie University, Sydney, New South Wales, Australia; Biomolecular Discovery Research Centre, Macquarie University, Sydney, New South Wales, Australia.
Benjamin L ParkerDepartment of Physiology, University of Melbourne, Melbourne, Victoria, Australia.
Vignesh VenkatakrishnanDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Regis DieckmannDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Oliver C GrantComplex Carbohydrate Research Center, University of Georgia, Athens, Georgia, USA.
Johan BylundDepartment of Oral Microbiology and Immunology, Institute of Odontology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Alison RodgerDepartment of Molecular Sciences, Macquarie University, Sydney, New South Wales, Australia; Biomolecular Discovery Research Centre, Macquarie University, Sydney, New South Wales, Australia.
Robert J WoodsComplex Carbohydrate Research Center, University of Georgia, Athens, Georgia, USA.
Anna Karlsson-BengtssonDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden.
Weston B StruweDepartment of Chemistry, University of Oxford, Oxford, United Kingdom.
Morten Thaysen-AndersenDepartment of Molecular Sciences, Macquarie University, Sydney, New South Wales, Australia; Biomolecular Discovery Research Centre, Macquarie University, Sydney, New South Wales, Australia. Electronic address: morten.andersen@mq.edu.au.
Macquarie University · AUUniversity of Gothenburg · SEUniversity of Oxford · GBUniversity of Georgia · USChalmers University of Technology · SECordlife (Singapore) · SGThe University of Melbourne · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Myeloperoxidase (MPO) plays essential roles in neutrophil-mediated immunity via the generation of reactive oxidation products. Complex carbohydrates decorate MPO at discrete sites, but their functional relevance remains elusive. To this end, we have characterised the structure-biosynthesis-activity relationship of neutrophil MPO (nMPO). Mass spectrometry demonstrated that nMPO carries both characteristic under-processed and hyper-truncated glycans. Occlusion of the Asn355/Asn391-glycosylation sites and the Asn323-/Asn483-glycans, located in the MPO dimerisation zone, was found to affect the local glycan processing, thereby providing a molecular basis of the site-specific nMPO glycosylation. Native mass spectrometry, mass photometry and glycopeptide profiling revealed significant molecular complexity of diprotomeric nMPO arising from heterogeneous glycosylation, oxidation, chlorination and polypeptide truncation variants and a previously unreported low-abundance monoprotomer. Longitudinal profiling of maturing, mature, granule-separated and pathogen-stimulated neutrophils demonstrated that nMPO is dynamically expressed during granulopoiesis, unevenly distributed across granules and degranulated upon activation. We also show that proMPO-to-MPO maturation occurs during early/mid-stage granulopoiesis. While similar global MPO glycosylation was observed across conditions, the conserved Asn355-/Asn391-sites displayed elevated glycan hyper-truncation, which correlated with higher enzyme activities of MPO in distinct granule populations. Enzymatic trimming of the Asn355-/Asn391-glycans recapitulated the activity gain and showed that nMPO carrying hyper-truncated glycans at these positions exhibits increased thermal stability, polypeptide accessibility and ceruloplasmin-mediated inhibition potential relative to native nMPO. Finally, molecular modelling revealed that hyper-truncated Asn355-glycans positioned in the MPO-ceruloplasmin interface are critical for uninterrupted inhibition. Here, through an innovative and comprehensive approach, we report novel functional roles of MPO glycans, providing new insight into neutrophil-mediated immunity.

Indexed as

Cytoplasmic GranulesGlycopeptidesGlycosylationHumansNeutrophilsPeroxidasePolysaccharidesGlycopeptidesPeroxidasePolysaccharidesactivitybiosynthesisceruloplasmindegranulationgranulegranulopoiesisinhibitionmyeloperoxidaseneutrophilN-glycosylation

Identifiers

PMID33273015
PMCPMC7857493
OpenAlexW3108967278

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.