Evidence map›Paper›PMID 24282309›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2013

Cytokine Spatzle binds to the Drosophila immunoreceptor Toll with a neurotrophin-like specificity and couples receptor activation.

Miranda Lewis, Christopher J Arnot, Helen Beeston, Airlie McCoy, Alison E Ashcroft, Nicholas J Gay, Monique Gangloff

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.2field-weighted citation impact, top 13% 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

23 citing papers in PubMed, 50 citations in OpenAlex.

  1. Article
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  9. Immunological Roles ofInternational journal of molecular sciences · 2022
    Article
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  11. Review
  12. Article
  13. Article
  14. Article
  15. Spz/Toll-6 signal guides organotropic metastasis inDisease models & mechanisms · 2019
    Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. 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

7 authors at 3 institutions in 1 country.

Miranda LewisDepartment of Biochemistry, University of Cambridge, Cambridge CB2 1GA, United Kingdom.
Christopher J Arnot
Helen Beeston
Airlie McCoy
Alison E Ashcroft
Nicholas J Gay
Monique Gangloff
University of Cambridge · GBInstitute of Structural and Molecular Biology · GBUniversity of Leeds · GB

Funding

Biotechnology and Biological Sciences Research Council BB/F01614/XMedical Research Council G1000133Wellcome Trust 100321Wellcome Trust WT 075099/Z/04/ZWellcome Trust WT081744/Z/06/Z
6 · The paper itself

Abstract

Drosophila Toll functions in embryonic development and innate immunity and is activated by an endogenous ligand, Spätzle (Spz). The related Toll-like receptors in vertebrates also function in immunity but are activated directly by pathogen-associated molecules such as bacterial endotoxin. Here, we present the crystal structure at 2.35-Å resolution of dimeric Spz bound to a Toll ectodomain encompassing the first 13 leucine-rich repeats. The cystine knot of Spz binds the concave face of the Toll leucine-rich repeat solenoid in an area delineated by N-linked glycans and induces a conformational change. Mutagenesis studies confirm that the interface observed in the crystal structure is relevant for signaling. The asymmetric binding mode of Spz to Toll is similar to that of nerve growth factor (NGF) in complex with the p75 neurotrophin receptor but is distinct from that of microbial ligands bound to the Toll-like receptors. Overall, this study indicates an allosteric signaling mechanism for Toll in which ligand binding to the N terminus induces a conformational change that couples to homodimerization of juxtamembrane structures in the Toll ectodomain C terminus.

Indexed as

AnimalsCrystallography, X-RayDrosophila melanogasterDrosophila ProteinsEndotoxinsImmunity, InnateNerve Growth FactorProtein BindingProtein MultimerizationProtein Structure, QuaternaryReceptor, Nerve Growth FactorRepetitive Sequences, Amino AcidToll-Like ReceptorsDrosophila ProteinsEndotoxinsNerve Growth FactorReceptor, Nerve Growth Factorspz protein, DrosophilaTl protein, DrosophilaToll-Like Receptorscrystallographyisothermal titration calorimetrymass spectrometrySpz ligandToll receptor

Identifiers

PMID24282309
PMCPMC3870763
OpenAlexW1998446009

What OpenQuestion holds

Textmetadata
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.