Evidence map›Paper›PMID 29596914›Full record

ArticleJournal of molecular biology2018

VLR Recognition of TLR5 Expands the Molecular Characterization of Protein Antigen Binding by Non-Ig-based Antibodies.

Robin J Gunn, Brantley R Herrin, Sharmistha Acharya, Max D Cooper, Ian A Wilson

Abstract read
In one paragraph

Article in Journal of molecular biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.8field-weighted citation impact, top 31% 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

11 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Structure of fish Toll-like receptors (TLR) and NOD-like receptors (NLR).International journal of biological macromolecules · 2020
    Review
  8. Article
  9. 50 Years of structural immunology.The Journal of biological chemistry
    Review
  10. Article
  11. Review
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.

Robin J GunnDepartment of Integrative Structural and Computational Biology and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Brantley R HerrinEmory Vaccine Center and Department of Pathology and Laboratory Medicine, Emory University, 1462 Clifton Road North-East, Atlanta, GA 30322, USA.
Sharmistha AcharyaDepartment of Integrative Structural and Computational Biology and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Max D CooperEmory Vaccine Center and Department of Pathology and Laboratory Medicine, Emory University, 1462 Clifton Road North-East, Atlanta, GA 30322, USA.
Ian A WilsonDepartment of Integrative Structural and Computational Biology and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: wilson@scripps.edu.
Scripps Research Institute · USEmory University · US

Funding

X-ray Absorption Spectroscopy (XAS) pp.711-759P41GM103393 · NIGMS · STANFORD UNIVERSITY · PI HODGSON, KEITH O · 2012 to 2019
$30.6M
Characterization of the Lamprey Adaptive Immune SystemR01AI072435 · NIAID · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Max Dale Cooper · 2007 to 2026
$8.1M
Overall Priority Score P41GM103694 · NIGMS · EMORY UNIVERSITY · PI CUMMINGS, RICHARD D · 2013 to 2018
$6.9M
Structural basis of TLR and NLR recognition and signalingR01AI042266 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI WILSON, IAN A · 1998 to 2017
$3.7M
Smart Anti-Glycan Reagents to Generate the Human Glycome Atlas-SupplementU01CA199882 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI CUMMINGS, RICHARD D, MERNAUGH, RAYMOND L · 2015 to 2017
$2.0M
NCI NIH HHS U01 CA199882NIAID NIH HHS R01 AI042266NIAID NIH HHS R01 AI072435NIGMS NIH HHS P41 GM103393NIGMS NIH HHS P41 GM103694
6 · The paper itself

Abstract

Variable lymphocyte receptors (VLRs) are unconventional adaptive immune receptors relatively recently discovered in the phylogenetically ancient jawless vertebrates, lamprey and hagfish. VLRs bind antigens using a leucine-rich repeat fold and are the only known adaptive immune receptors that do not utilize an immunoglobulin fold for antigen recognition. While immunoglobulin antibodies have been studied extensively, there are comparatively few studies on antigen recognition by VLRs, particularly for protein antigens. Here we report isolation, functional and structural characterization of three VLRs that bind the protein toll-like receptor 5 (TLR5) from zebrafish. Two of the VLRs block binding of TLR5 to its cognate ligand flagellin in functional assays using reporter cells. Co-crystal structures revealed that these VLRs bind to two different epitopes on TLR5, both of which include regions involved in flagellin binding. Our work here demonstrates that the lamprey adaptive immune system can be used to generate high-affinity VLR clones that recognize different epitopes and differentially impact natural ligand binding to a protein antigen.

Indexed as

AnimalsAntibodies, MonoclonalBinding SitesCrystallography, X-RayEpitopesFlagellinHumansImmunizationJurkat CellsModels, MolecularPetromyzonProtein ConformationToll-Like Receptor 5ZebrafishZebrafish ProteinsAntibodies, MonoclonalEpitopesFlagellinToll-Like Receptor 5Zebrafish Proteinsantigen bindinginnate immunityleucine-rich repeatprotein–protein complexX-ray crystallography

Identifiers

PMID29596914
PMCPMC5915902
OpenAlexW2792299298

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.