Evidence map›Paper›PMID 25650935›Full record

ArticleBiophysical journal2015

The conundrum of the high-affinity NGF binding site formation unveiled?

Sonia Covaceuszach, Petr V Konarev, Alberto Cassetta, Francesca Paoletti, Dmitri I Svergun, Doriano Lamba, Antonino Cattaneo

Open access · bronzeAbstract read
In one paragraph

Article in Biophysical journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.1field-weighted citation impact, top 26% 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

18 citing papers in PubMed, 22 citations in OpenAlex.

  1. Review
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  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
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  11. Fast-diffusing p75Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Journal of applied crystallography · 2017
    Article
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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 2 countries.

Sonia CovaceuszachIstituto di Cristallografia, Consiglio Nazionale delle Ricerche, Trieste, Italy.
Petr V KonarevEuropean Molecular Biology Laboratory, Hamburg Outstation, Hamburg, Germany; Institute of Crystallography, Russian Academy of Sciences, Moscow, Russia.
Alberto CassettaIstituto di Cristallografia, Consiglio Nazionale delle Ricerche, Trieste, Italy.
Francesca PaolettiEuropean Brain Research Institute, Roma, Italy.
Dmitri I SvergunEuropean Molecular Biology Laboratory, Hamburg Outstation, Hamburg, Germany.
Doriano LambaIstituto di Cristallografia, Consiglio Nazionale delle Ricerche, Trieste, Italy. Electronic address: doriano.lamba@ts.ic.cnr.it.
Antonino CattaneoEuropean Brain Research Institute, Roma, Italy; Scuola Normale Superiore, Pisa, Italy. Electronic address: antonino.cattaneo@sns.it.
Institute of Crystallography · ITEuropean Brain Research Institute · ITEuropean Molecular Biology Laboratory · DE

Funding

Telethon GGP11179
6 · The paper itself

Abstract

The homodimer NGF (nerve growth factor) exerts its neuronal activity upon binding to either or both distinct transmembrane receptors TrkA and p75(NTR). Functionally relevant interactions between NGF and these receptors have been proposed, on the basis of binding and signaling experiments. Namely, a ternary TrkA/NGF/p75(NTR) complex is assumed to be crucial for the formation of the so-called high-affinity NGF binding sites. However, the existence, on the cell surface, of direct extracellular interactions is still a matter of controversy. Here, supported by a small-angle x-ray scattering solution study of human NGF, we propose that it is the oligomerization state of the secreted NGF that may drive the formation of the ternary heterocomplex. Our data demonstrate the occurrence in solution of a concentration-dependent distribution of dimers and dimer of dimers. A head-to-head molecular assembly configuration of the NGF dimer of dimers has been validated. Overall, these findings prompted us to suggest a new, to our knowledge, model for the transient ternary heterocomplex, i.e., a TrkA/NGF/p75(NTR) ligand/receptors molecular assembly with a (2:4:2) stoichiometry. This model would neatly solve the problem posed by the unconventional orientation of p75(NTR) with respect to TrkA, as being found in the crystal structures of the TrkA/NGF and p75(NTR)/NGF complexes.

Indexed as

Molecular Dynamics SimulationBinding SitesHumansHydrogen BondingNerve Growth FactorProtein MultimerizationReceptor, trkAScattering, Small AngleX-Ray DiffractionNerve Growth FactorReceptor, trkA

Identifiers

PMID25650935
PMCPMC4317559
OpenAlexW2010808063

What OpenQuestion holds

Textmetadata
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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.