Evidence map›Paper›PMID 38702390›Full record

ArticleMolecular systems biology2024

Systematic identification of structure-specific protein-protein interactions.

Aleš Holfeld, Dina Schuster, Fabian Sesterhenn, Alison K Gillingham, Patrick Stalder, Walther Haenseler, Inigo Barrio-Hernandez, Dhiman Ghosh, Jane Vowles, Sally A Cowley and 9 more

Abstract read
In one paragraph

Article in Molecular systems biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
–field-weighted citation impact
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

17 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. State-of-the-Art and Future Directions in Structural Proteomics.Molecular & cellular proteomics : MCP · 2025
    Review
  9. Article
  10. Article
  11. Analysis of Limited Proteolysis-Coupled Mass Spectrometry Data.Molecular & cellular proteomics : MCP · 2025
    Article
  12. Article
  13. Review
  14. Article
  15. Review
  16. Structural basis of calmodulin modulation of the rod cyclic nucleotide-gated channel.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  17. 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

19 authors.

Aleš HolfeldInstitute of Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland.
Dina SchusterInstitute of Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0001-6611-8237
Fabian SesterhennInstitute of Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland.
Alison K GillinghamMRC Laboratory of Molecular Biology, Cambridge, UK.ORCID http://orcid.org/0009-0000-3835-2333
Patrick StalderInstitute of Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland.
Walther HaenselerInstitute of Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0003-4868-3704
Inigo Barrio-HernandezEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.ORCID http://orcid.org/0000-0002-5686-0451
Dhiman GhoshLaboratory of Physical Chemistry, ETH Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0003-2087-8075
Jane VowlesJames and Lillian Martin Centre for Stem Cell Research, Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Sally A CowleyJames and Lillian Martin Centre for Stem Cell Research, Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0003-0297-6675
Luise NagelCluster of Excellence Cellular Stress Responses in Aging-associated Diseases (CECAD), University of Cologne, Cologne, Germany.ORCID http://orcid.org/0000-0001-8844-7234
Basavraj KhanppnavarInstitute of Molecular Biology and Biophysics, Department of Biology, ETH Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0002-6637-3550
Tetiana SerdiukInstitute of Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland.
Pedro BeltraoInstitute of Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0002-2724-7703
Volodymyr M KorkhovInstitute of Molecular Biology and Biophysics, Department of Biology, ETH Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0002-0962-9433
Sean MunroMRC Laboratory of Molecular Biology, Cambridge, UK.ORCID http://orcid.org/0000-0001-6160-5773
Roland RiekLaboratory of Physical Chemistry, ETH Zurich, Zurich, Switzerland.
Natalie de SouzaInstitute of Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0003-4286-8951
Paola PicottiInstitute of Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland. picotti@imsb.biol.ethz.ch.ORCID http://orcid.org/0000-0002-4109-3552

Funding

EC | European Research Council (ERC) 866004European Proteomics Infrastructure Consortium providing access (EPIC-XS) 823839European Research Council 866004Medical Research Council MC_U105178783Swiss National Science Foundation 184951Swiss National Science Foundation CRSII5_177195
6 · The paper itself

Abstract

The physical interactome of a protein can be altered upon perturbation, modulating cell physiology and contributing to disease. Identifying interactome differences of normal and disease states of proteins could help understand disease mechanisms, but current methods do not pinpoint structure-specific PPIs and interaction interfaces proteome-wide. We used limited proteolysis-mass spectrometry (LiP-MS) to screen for structure-specific PPIs by probing for protease susceptibility changes of proteins in cellular extracts upon treatment with specific structural states of a protein. We first demonstrated that LiP-MS detects well-characterized PPIs, including antibody-target protein interactions and interactions with membrane proteins, and that it pinpoints interfaces, including epitopes. We then applied the approach to study conformation-specific interactors of the Parkinson's disease hallmark protein alpha-synuclein (aSyn). We identified known interactors of aSyn monomer and amyloid fibrils and provide a resource of novel putative conformation-specific aSyn interactors for validation in further studies. We also used our approach on GDP- and GTP-bound forms of two Rab GTPases, showing detection of differential candidate interactors of conformationally similar proteins. This approach is applicable to screen for structure-specific interactomes of any protein, including posttranslationally modified and unmodified, or metabolite-bound and unbound protein states.

Indexed as

alpha-SynucleinAmyloidHumansMass SpectrometryParkinson DiseaseProtein BindingProtein ConformationProtein Interaction MappingProtein Interaction MapsProteolysisProteomerab GTP-Binding Proteinsalpha-SynucleinAmyloidProteomerab GTP-Binding ProteinsLimited ProteolysisMass SpectrometryProtein–protein InteractionsStructural ProteomicsStructure-Specific Interactions

Identifiers

PMID38702390
PMCPMC11148107

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Registered trials

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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.