Evidence map›Paper›PMID 25048602›Full record

ArticleNature communications2014

Protein painting reveals solvent-excluded drug targets hidden within native protein-protein interfaces.

Alessandra Luchini, Virginia Espina, Lance A Liotta

Open access · bronzeAbstract read
In one paragraph

Article in Nature communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
4.6field-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

41 citing papers in PubMed, 64 citations in OpenAlex.

  1. Multiplex mapping of protein-protein interaction interfaces.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  2. Article
  3. State-of-the-Art and Future Directions in Structural Proteomics.Molecular & cellular proteomics : MCP · 2025
    Review
  4. Multiplex mapping of protein-protein interaction interfaces.bioRxiv : the preprint server for biology · 2025
    Article
  5. Analysis of Limited Proteolysis-Coupled Mass Spectrometry Data.Molecular & cellular proteomics : MCP · 2025
    Article
  6. Article
  7. Laser capture microdissection.Nature reviews. Methods primers · 2025
    Article
  8. Article
  9. Review
  10. Article
  11. Article
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  15. Review
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  19. Article
  20. Molecular basis for protein-protein interactions.Beilstein journal of organic chemistry · 2021
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Alessandra LuchiniCenter for Applied Proteomics and Molecular Medicine, George Mason University, 10900 University Boulevard, Manassas, Virginia 20110, USA.
Virginia EspinaCenter for Applied Proteomics and Molecular Medicine, George Mason University, 10900 University Boulevard, Manassas, Virginia 20110, USA.
Lance A LiottaCenter for Applied Proteomics and Molecular Medicine, George Mason University, 10900 University Boulevard, Manassas, Virginia 20110, USA.
George Mason University · US

Funding

Resource for Biocomputing Visualization and InformaticsP41GM103311 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERRIN, THOMAS E · 2012 to 2017
$8.2M
Probes to target the 3-way hotspot of IL1RacP to abolish aberrant interleukin inflammationR01AR068436 · NIAMS · GEORGE MASON UNIVERSITY · PI LIOTTA, LANCE ALLEN · 2015 to 2017
$1.7M
Nanotrap technology for one step preservation and amplification of cancer biomarkR33CA173359 · NCI · GEORGE MASON UNIVERSITY · PI LIOTTA, LANCE ALLEN · 2012 to 2014
$1.1M
Protein Painting reveals hidden protein-protein interaction domainsR21CA177535 · NCI · GEORGE MASON UNIVERSITY · PI LIOTTA, LANCE ALLEN · 2013 to 2014
$482k
A non-invasive nanotechnology-based skin patch for multiplexed diagnosticsR21AR061075 · NIAMS · GEORGE MASON UNIVERSITY · PI LIOTTA, LANCE ALLEN · 2011 to 2012
$360k
NCI NIH HHS NIH NCI 1R21CA177535-01NCI NIH HHS NIH NCI 1R33CA173359-01NCI NIH HHS R21 CA177535NCI NIH HHS R33 CA173359NIAMS NIH HHS NIH NIAMS 1R21AR061075-01NIAMS NIH HHS R01 AR068436NIAMS NIH HHS R21 AR061075NIGMS NIH HHS P41 GM103311PHS HHS NIGMS P41-GM103311
6 · The paper itself

Abstract

Identifying the contact regions between a protein and its binding partners is essential for creating therapies that block the interaction. Unfortunately, such contact regions are extremely difficult to characterize because they are hidden inside the binding interface. Here we introduce protein painting as a new tool that employs small molecules as molecular paints to tightly coat the surface of protein-protein complexes. The molecular paints, which block trypsin cleavage sites, are excluded from the binding interface. Following mass spectrometry, only peptides hidden in the interface emerge as positive hits, revealing the functional contact regions that are drug targets. We use protein painting to discover contact regions between the three-way interaction of IL1β ligand, the receptor IL1RI and the accessory protein IL1RAcP. We then use this information to create peptides and monoclonal antibodies that block the interaction and abolish IL1β cell signalling. The technology is broadly applicable to discover protein interaction drug targets.

Indexed as

Protein Interaction Domains and MotifsAmino Acid SequenceAnimalsAntibodies, MonoclonalColoring AgentsInterleukin-1betaInterleukin-1 Receptor Accessory ProteinMass SpectrometryMiceModels, MolecularMolecular Sequence DataMolecular Targeted TherapyPeptidesProtein ConformationProtein Interaction MappingReceptors, Interleukin-1 Type IAntibodies, MonoclonalColoring AgentsInterleukin-1betaInterleukin-1 Receptor Accessory ProteinPeptidesReceptors, Interleukin-1 Type ISolventsTrypsin

Identifiers

PMID25048602
PMCPMC4109009
OpenAlexW2066297967

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.