Evidence map›Paper›PMID 30597163›Full record

ArticleJournal of molecular biology2019

Fluorescent Trimeric Hemagglutinins Reveal Multivalent Receptor Binding Properties.

Nikoloz Nemanichvili, Ilhan Tomris, Hannah L Turner, Ryan McBride, Oliver C Grant, Roosmarijn van der Woude, Mohammed H Aldosari, Roland J Pieters, Robert J Woods, James C Paulson and 4 more

Open access · hybridAbstract read
In one paragraph

Article in Journal of molecular biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing 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

32 citing papers in PubMed, 56 citations in OpenAlex.

  1. Article
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  4. Human coronavirus HKU1 neutralization by glycan receptor mimicry.bioRxiv : the preprint server for biology · 2025
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  5. The Q226L mutation can convert a highly pathogenic H5 2.3.4.4e virus to bind human-type receptors.Proceedings of the National Academy of Sciences of the United States of America · 2025
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  6. Article
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  8. Article
  9. Article
  10. Chemoenzymatic Synthesis of Tri-antennary N-Glycans Terminating in Sialyl-LewisChemistry (Weinheim an der Bergstrasse, Germany) · 2024
    Article
  11. The HCoV-HKU1 N-terminal domain binds a wide range of 9-bioRxiv : the preprint server for biology · 2024
    Article
  12. ComplexJournal of virology · 2024
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Journal of virology · 2022
    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

14 authors at 3 institutions in 3 countries.

Nikoloz NemanichviliPathology Division, Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, 3584, CL, Utrecht, the Netherlands.
Ilhan TomrisDepartment of Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584, CG, Utrecht, the Netherlands.
Hannah L TurnerDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Ryan McBrideDepartment of Molecular Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA; Department of Immunology & Microbiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Oliver C GrantComplex Carbohydrate Research Center, University of Georgia, 315 Riverbend Rd, Athens, GA 30602, USA.
Roosmarijn van der WoudeDepartment of Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584, CG, Utrecht, the Netherlands.
Mohammed H AldosariDepartment of Pharmaceutical Sciences, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584, CG, Utrecht, the Netherlands; Drug sector, Saudi Food and Drug Authority, Riyadh, Saudi Arabia.
Roland J PietersDepartment of Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584, CG, Utrecht, the Netherlands.
Robert J WoodsComplex Carbohydrate Research Center, University of Georgia, 315 Riverbend Rd, Athens, GA 30602, USA.
James C PaulsonDepartment of Molecular Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA; Department of Immunology & Microbiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Geert-Jan BoonsDepartment of Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584, CG, Utrecht, the Netherlands; Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Rd, Athens, GA 30602, USA.
Andrew B WardDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Monique H VerheijePathology Division, Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, 3584, CL, Utrecht, the Netherlands. Electronic address: m.h.verheije@uu.nl.
Robert P de VriesDepartment of Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584, CG, Utrecht, the Netherlands. Electronic address: r.vries@uu.nl.
Utrecht University · NLScripps Research Institute · USUniversity of Georgia · US

Funding

Structural Basis of Immune Recognition of Glycosylated AntigensU54GM062116 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI PAULSON, JAMES C · 2001 to 2010
$80.3M
TR&D3. Approaches to Proteoglycan Function at Biochemical and Cellular LevelsP41GM103390 · NIGMS · UNIVERSITY OF GEORGIA · PI MOREMEN, KELLEY W. · 2012 to 2019
$14.5M
REGULATION OF SIALOSIDE EXPRESSION IN LEUKOCYTESR01AI050143 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI PAULSON, JAMES C · 2003 to 2018
$7.0M
Influenza virus receptors on human airway epithelial cellsR01AI114730 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI PAULSON, JAMES C · 2015 to 2023
$5.1M
Tools to enable non-specialists to model glycoconjugates and glycan-protein interactionsU01CA207824 · NCI · UNIVERSITY OF GEORGIA · PI FOLEY, B. LACHELE, WOODS, ROBERT J · 2016 to 2018
$1.7M
NCI NIH HHS U01 CA207824NIAID NIH HHS R01 AI050143NIAID NIH HHS R01 AI114730NIGMS NIH HHS P41 GM103390NIGMS NIH HHS U54 GM062116
6 · The paper itself

Abstract

Influenza A virus carries hundreds of trimeric hemagglutinin (HA) proteins on its viral envelope that interact with various sialylated glycans on a host cell. This interaction represents a multivalent binding event that is present in all the current receptor binding assays, including those employing viruses or precomplexed HA trimers. To study the nature of such multivalent binding events, we fused a superfolder green fluorescent protein (sfGFP) to the C-terminus of trimeric HA to allow for direct visualization of HA-receptor interactions without the need for additional fluorescent antibodies. The multivalent binding of the HA-sfGFP proteins was studied using glycan arrays and tissue staining. The HA-sfGFP with human-type receptor specificity was able to bind to a glycan array as the free trimer. In contrast, the HA-sfGFP with avian-type receptor specificity required multimerization by antibodies before binding to glycans on the glycan array could be observed. Interestingly, multimerization was not required for binding to tissues. The array data may be explained by the possible bivalent binding mode of a single human-specific HA trimer to complex branched N-glycans, which is not possible for the avian-specific HA due to geometrical constrains of the binding sites. The fact that this specificity pattern changes upon interaction with a cell surface probably represents the enhanced amount of glycan orientations and variable densities versus those on the glycan array.

Indexed as

AnimalsBinding SitesBirdsHemagglutinin Glycoproteins, Influenza VirusHumansInfluenza A virusInfluenza, HumanInfluenza in BirdsPolysaccharidesProtein BindingReceptors, Cell SurfaceHemagglutinin Glycoproteins, Influenza VirusPolysaccharidesReceptors, Cell Surfaceattachment proteinbidentateInfluenzamultivalentprecomplexing

Identifiers

PMID30597163
PMCPMC6397626
OpenAlexW2908395697

What OpenQuestion holds

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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.