Evidence map›Paper›PMID 36402845›Full record

ArticleNature communications2022

Structure of the human heparan sulfate polymerase complex EXT1-EXT2.

Francisco Leisico, Juneina Omeiri, Christine Le Narvor, Joël Beaudouin, Michael Hons, Daphna Fenel, Guy Schoehn, Yohann Couté, David Bonnaffé, Rabia Sadir and 2 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
3.7field-weighted citation impact, top 6% 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

28 citing papers in PubMed, 36 citations in OpenAlex.

  1. Article
  2. Spatial Glyco-Codes Define Human Liver Pathology and Progression.bioRxiv : the preprint server for biology · 2026
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  10. Endothelial glycocalyx glycan expression in lymphatic vasculature in mice.Frontiers in cell and developmental biology · 2026
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  11. Hedgehog and Drosophila germ cell migration.Development (Cambridge, England) · 2025
    Review
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  14. The Intersection of Glycosylation and Ferroptosis in Cancer.Antioxidants (Basel, Switzerland) · 2025
    Review
  15. Article
  16. Article
  17. World journal of gastroenterology · 2025
    Article
  18. Structural glycobiology - from enzymes to organelles.Biochemical Society transactions · 2025
    Review
  19. 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

12 authors at 2 institutions in 1 country.

Francisco Leisico *Institut de Biologie Structurale, UMR 5075, University Grenoble Alpes, CNRS, CEA, 38000, Grenoble, France.ORCID 0000-0002-4672-4659
Juneina Omeiri *Institut de Biologie Structurale, UMR 5075, University Grenoble Alpes, CNRS, CEA, 38000, Grenoble, France.ORCID 0000-0003-0607-1179
Christine Le NarvorUniversité Paris-Saclay, CNRS, Institut de chimie moléculaire et des matériaux d'Orsay, 91405, Orsay, France.
Joël BeaudouinInstitut de Biologie Structurale, UMR 5075, University Grenoble Alpes, CNRS, CEA, 38000, Grenoble, France.
Michael HonsEuropean Molecular Biology Laboratory (EMBL), Grenoble Outstation, 71 avenue des Martyrs, 38042, Grenoble, France.ORCID 0000-0002-8317-7631
Daphna FenelInstitut de Biologie Structurale, UMR 5075, University Grenoble Alpes, CNRS, CEA, 38000, Grenoble, France.
Guy SchoehnInstitut de Biologie Structurale, UMR 5075, University Grenoble Alpes, CNRS, CEA, 38000, Grenoble, France.ORCID 0000-0002-1459-3201
Yohann CoutéUniversity Grenoble Alpes, INSERM, CEA, UMR BioSanté U1292, CNRS, CEA, FR2048, 38000, Grenoble, France.ORCID 0000-0003-3896-6196
David BonnafféUniversité Paris-Saclay, CNRS, Institut de chimie moléculaire et des matériaux d'Orsay, 91405, Orsay, France.ORCID 0000-0001-9361-2599
Rabia SadirInstitut de Biologie Structurale, UMR 5075, University Grenoble Alpes, CNRS, CEA, 38000, Grenoble, France.
Hugues Lortat-JacobInstitut de Biologie Structurale, UMR 5075, University Grenoble Alpes, CNRS, CEA, 38000, Grenoble, France. Hugues.Lortat-Jacob@ibs.fr.ORCID 0000-0002-9772-0762
Rebekka WildInstitut de Biologie Structurale, UMR 5075, University Grenoble Alpes, CNRS, CEA, 38000, Grenoble, France. Rebekka.Wild@ibs.fr.ORCID 0000-0003-2025-7228
Centre National de la Recherche Scientifique · FREuropean Molecular Biology Laboratory · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Heparan sulfates are complex polysaccharides that mediate the interaction with a broad range of protein ligands at the cell surface. A key step in heparan sulfate biosynthesis is catalyzed by the bi-functional glycosyltransferases EXT1 and EXT2, which generate the glycan backbone consisting of repeating N-acetylglucosamine and glucuronic acid units. The molecular mechanism of heparan sulfate chain polymerization remains, however, unknown. Here, we present the cryo-electron microscopy structure of human EXT1-EXT2, which reveals the formation of a tightly packed hetero-dimeric complex harboring four glycosyltransferase domains. A combination of in vitro and in cellulo mutational studies is used to dissect the functional role of the four catalytic sites. While EXT1 can catalyze both glycosyltransferase reactions, our results indicate that EXT2 might only have N-acetylglucosamine transferase activity. Our findings provide mechanistic insight into heparan sulfate chain elongation as a nonprocessive process and lay the foundation for future studies on EXT1-EXT2 function in health and disease.

Indexed as

Heparan SulfateN-AcetylglucosaminyltransferasesCryoelectron MicroscopyGlycosyltransferasesHumansNucleotidyltransferasesProteinsGlycosyltransferasesHeparan SulfateN-AcetylglucosaminyltransferasesNucleotidyltransferasesProteins

Identifiers

PMID36402845
PMCPMC9675754
OpenAlexW4309562772

What OpenQuestion holds

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LicenceCC BY
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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.