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Reliable identification of protein-protein interactions by crosslinking mass spectrometry

Author

Listed:
  • Swantje Lenz

    (Technische Universität Berlin)

  • Ludwig R. Sinn

    (Technische Universität Berlin)

  • Francis J. O’Reilly

    (Technische Universität Berlin)

  • Lutz Fischer

    (Technische Universität Berlin)

  • Fritz Wegner

    (Technische Universität Berlin)

  • Juri Rappsilber

    (Technische Universität Berlin
    University of Edinburgh)

Abstract

Protein-protein interactions govern most cellular pathways and processes, and multiple technologies have emerged to systematically map them. Assessing the error of interaction networks has been a challenge. Crosslinking mass spectrometry is currently widening its scope from structural analyses of purified multi-protein complexes towards systems-wide analyses of protein-protein interactions (PPIs). Using a carefully controlled large-scale analysis of Escherichia coli cell lysate, we demonstrate that false-discovery rates (FDR) for PPIs identified by crosslinking mass spectrometry can be reliably estimated. We present an interaction network comprising 590 PPIs at 1% decoy-based PPI-FDR. The structural information included in this network localises the binding site of the hitherto uncharacterised protein YacL to near the DNA exit tunnel on the RNA polymerase.

Suggested Citation

  • Swantje Lenz & Ludwig R. Sinn & Francis J. O’Reilly & Lutz Fischer & Fritz Wegner & Juri Rappsilber, 2021. "Reliable identification of protein-protein interactions by crosslinking mass spectrometry," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23666-z
    DOI: 10.1038/s41467-021-23666-z
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    Cited by:

    1. Andrea Fossati & Deepto Mozumdar & Claire Kokontis & Melissa Mèndez-Moran & Eliza Nieweglowska & Adrian Pelin & Yuping Li & Baron Guo & Nevan J. Krogan & David A. Agard & Joseph Bondy-Denomy & Daniell, 2023. "Next-generation proteomics for quantitative Jumbophage-bacteria interaction mapping," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Manuel Matzinger & Adrian Vasiu & Mathias Madalinski & Fränze Müller & Florian Stanek & Karl Mechtler, 2022. "Mimicked synthetic ribosomal protein complex for benchmarking crosslinking mass spectrometry workflows," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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