2. Academic Validation
  3. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome

Dual proteome-scale networks reveal cell-specific remodeling of the human interactome

  • Cell. 2021 May 27;184(11):3022-3040.e28. doi: 10.1016/j.cell.2021.04.011.
Edward L Huttlin 1,  Raphael J Bruckner 2,  Jose Navarrete-Perea 2,  Joe R Cannon 2,  Kurt Baltier 2,  Fana Gebreab 2,  Melanie P Gygi 2,  Alexandra Thornock 2,  Gabriela Zarraga 2,  Stanley Tam 2,  John Szpyt 2,  Brandon M Gassaway 2,  Alexandra Panov 2,  Hannah Parzen 2,  Sipei Fu 2,  Arvene Golbazi 2,  Eila Maenpaa 2,  Keegan Stricker 2,  Sanjukta Guha Thakurta 2,  Tian Zhang 2,  Ramin Rad 2,  Joshua Pan 3,  David P Nusinow 2,  Joao A Paulo 2,  Devin K Schweppe 2,  Laura Pontano Vaites 2,  J Wade Harper 4,  Steven P Gygi 5
Affiliations

Affiliations

  • 1 Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: edward_huttlin@hms.harvard.edu.
  • 2 Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
  • 3 Broad Institute, Cambridge, MA 02142, USA.
  • 4 Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: wade_harper@hms.harvard.edu.
  • 5 Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: steven_gygi@hms.harvard.edu.
PMID: 33961781 DOI: 10.1016/j.cell.2021.04.011
Abstract

Thousands of interactions assemble proteins into modules that impart spatial and functional organization to the cellular proteome. Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks. The first, BioPlex 3.0, results from affinity purification of 10,128 human proteins-half the proteome-in 293T cells and includes 118,162 interactions among 14,586 proteins. The second results from 5,522 immunoprecipitations in HCT116 cells. These networks model the interactome whose structure encodes protein function, localization, and complex membership. Comparison across cell lines validates thousands of interactions and reveals extensive customization. Whereas shared interactions reside in core complexes and involve essential proteins, cell-specific interactions link these complexes, "rewiring" subnetworks within each cell's interactome. Interactions covary among proteins of shared function as the proteome remodels to produce each cell's phenotype. Viewable interactively online through BioPlexExplorer, these networks define principles of proteome organization and enable unknown protein characterization.

Keywords

AP-MS; BioPlex; bioinformatics; cell specificity; computational biology; human interactome; network biology; protein interactions; proteomics; proteotypes.

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