Evidence map›Paper›PMID 30111543›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2018

N-glycan microheterogeneity regulates interactions of plasma proteins.

Di Wu, Weston B Struwe, David J Harvey, Michael A J Ferguson, Carol V Robinson

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
7.3field-weighted citation impact, top 2% 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

60 citing papers in PubMed, 112 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Journal of proteome research · 2025
    Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Uncovering the Role ofJournal of the American Chemical Society · 2023
    Article
  14. Dissecting the structural heterogeneity of proteins by native mass spectrometry.Protein science : a publication of the Protein Society · 2023
    Review
  15. Article
  16. Novel Biomarkers for Diagnosis and Monitoring of Immune Thrombocytopenia.International journal of molecular sciences · 2023
    Review
  17. Article
  18. Article
  19. Systems-Wide Site-Specific Analysis of Glycoproteins.Methods in molecular biology (Clifton, N.J.) · 2023
    Article
  20. Article
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

5 authors at 2 institutions in 1 country.

Di WuDepartment of Chemistry, University of Oxford, Oxford OX1 3QZ, United Kingdom.
Weston B StruweDepartment of Chemistry, University of Oxford, Oxford OX1 3QZ, United Kingdom.
David J HarveyTarget Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, United Kingdom.
Michael A J FergusonWellcome Centre for Anti-Infectives Research, School of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom.
Carol V RobinsonDepartment of Chemistry, University of Oxford, Oxford OX1 3QZ, United Kingdom; carol.robinson@chem.ox.ac.uk.ORCID 0000-0001-7829-5505
University of Oxford · GBUniversity of Dundee · GB

Funding

European Research Council 641317Medical Research Council MR/N020413/1Wellcome TrustWellcome Trust 104633/Z/14/Z
6 · The paper itself

Abstract

Altered glycosylation patterns of plasma proteins are associated with autoimmune disorders and pathogenesis of various cancers. Elucidating glycoprotein microheterogeneity and relating subtle changes in the glycan structural repertoire to changes in protein-protein, or protein-small molecule interactions, remains a significant challenge in glycobiology. Here, we apply mass spectrometry-based approaches to elucidate the global and site-specific microheterogeneity of two plasma proteins: α1-acid glycoprotein (AGP) and haptoglobin (Hp). We then determine the dissociation constants of the anticoagulant warfarin to different AGP glycoforms and reveal how subtle N-glycan differences, namely, increased antennae branching and terminal fucosylation, reduce drug-binding affinity. Conversely, similar analysis of the haptoglobin-hemoglobin (Hp-Hb) complex reveals the contrary effects of fucosylation and N-glycan branching on Hp-Hb interactions. Taken together, our results not only elucidate how glycoprotein microheterogeneity regulates protein-drug/protein interactions but also inform the pharmacokinetics of plasma proteins, many of which are drug targets, and whose glycosylation status changes in various disease states.

Indexed as

Models, ChemicalGlucansHaptoglobinsHumansOrosomucoidWarfarinGlucansHaptoglobinsOrosomucoidWarfaringlycoproteinmass spectrometryprotein interactions

Identifiers

PMID30111543
PMCPMC6126716
OpenAlexW2885864932

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.