Evidence map›Paper›PMID 20036257›Full record

ArticleJournal of molecular biology2010

Molecular and structural insight into proNGF engagement of p75NTR and sortilin.

Dan Feng, Taeho Kim, Engin Ozkan, Matthew Light, Risa Torkin, Kenneth K Teng, Barbara L Hempstead, K Christopher Garcia

Abstract read
In one paragraph

Article in Journal of molecular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
2.0field-weighted citation impact, top 16% 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

59 citing papers in PubMed, 103 citations in OpenAlex.

  1. Review
  2. Nerve growth factor receptor (NGFR): A key player in glioblastoma progression.Biochimica et biophysica acta. Reviews on cancer · 2026
    Review
  3. Article
  4. Review
  5. P75iScience · 2025
    Article
  6. Review
  7. Article
  8. Article
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  14. Review
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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

8 authors at 3 institutions in 1 country.

Dan FengDepartment of Cellular and Molecular Physiology, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Taeho Kim
Engin Ozkan
Matthew Light
Risa Torkin
Kenneth K Teng
Barbara L Hempstead
K Christopher Garcia
Cornell University · USHoward Hughes Medical Institute · USStanford University · US

Funding

Structure-based engineering of immune cytokine signalingR01AI051321 · NIAID · STANFORD UNIVERSITY · PI Kenan Christopher GARCIA · 2002 to 2026
$5.6M
Cellular and Molecular Mechanisms of Neurotrophin ActionsR01NS057627 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI TENG, KENNETH KIEN-FENG · 2007 to 2011
$1.6M
Howard Hughes Medical InstituteNIAID NIH HHS R01 AI051321NIAID NIH HHS R01-AI51321NINDS NIH HHS R01 NS057627NINDS NIH HHS R0I NS057627NINDS NIH HHS R0I NS30658
6 · The paper itself

Abstract

Nerve growth factor (NGF) is initially synthesized as a precursor, proNGF, that is cleaved to release its C-terminal mature form. Recent studies suggested that proNGF is not an inactive precursor but acts as a signaling ligand distinct from its mature counterpart. proNGF and mature NGF initiate opposing biological responses by utilizing both distinct and shared receptor components. In this study, we carried out structural and biochemical characterization of proNGF interactions with p75NTR and sortilin. We crystallized proNGF complexed to p75NTR and present the structure at 3.75-A resolution. The structure reveals a 2:2 symmetric binding mode, as compared with the asymmetric structure of a previously reported crystal structure of mature NGF complexed to p75NTR and the 2:2 symmetric complex of neurotrophin-3 (NT-3) and p75NTR. Here, we discuss the possible origins and implications of the different stoichiometries. In the proNGF-p75NTR complex, the pro regions of proNGF are mostly disordered and two hairpin loops (loop 2) at the top of the NGF dimer have undergone conformational changes in comparison with mature NT structures, suggesting possible interactions with the propeptide. We further explored the binding characteristics of proNGF to sortilin using surface plasmon resonance and cell-based assays and determined that calcium ions promote the formation of a stable ternary complex of proNGF-sortilin-p75NTR. These results, together with those of previous structural and mechanistic studies of NT-receptor interactions, suggest the potential for distinct signaling activities through p75NTR mediated by different NT-induced conformational changes.

Indexed as

Adaptor Proteins, Vesicular TransportAmino Acid SubstitutionAnimalsBinding SitesCalciumCell LineCrystallography, X-RayHumansIn Vitro TechniquesLigandsMiceModels, MolecularMultiprotein ComplexesMutagenesis, Site-DirectedNerve Growth FactorNerve Tissue ProteinsAdaptor Proteins, Vesicular TransportCalciumLigandsMultiprotein ComplexesNerve Growth FactorNerve Tissue ProteinsNgfr protein, ratpro-nerve growth factor, mouseProtein PrecursorsReceptors, Growth FactorReceptors, Nerve Growth FactorRecombinant ProteinsSortilin

Identifiers

PMID20036257
PMCPMC2847487
OpenAlexW2003205870

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.