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Huttlin EL, Bruckner RJ, Navarrete-Perea J, et al. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell. 2021;184(11):3022-3040.e28doi: 10.1016/j.cell.2021.04.011.
Huttlin, E. L., Bruckner, R. J., Navarrete-Perea, J., Cannon, J. R., Baltier, K., Gebreab, F., Gygi, M. P., Thornock, A., Zarraga, G., Tam, S., Szpyt, J., Gassaway, B. M., Panov, A., Parzen, H., Fu, S., Golbazi, A., Maenpaa, E., Stricker, K., Guha Thakurta, S., Zhang, T., Rad, R., Pan, J., Nusinow, D. P., Paulo, J. A., Schweppe, D. K., Vaites, L. P., Harper, J. W., & Gygi, S. P. (2021). Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell, 184(11), 3022-3040.e28. https://doi.org/10.1016/j.cell.2021.04.011
Huttlin, Edward L, et al. "Dual proteome-scale networks reveal cell-specific remodeling of the human interactome." Cell vol. 184,11 (2021): 3022-3040.e28. doi: https://doi.org/10.1016/j.cell.2021.04.011
Huttlin EL, Bruckner RJ, Navarrete-Perea J, Cannon JR, Baltier K, Gebreab F, Gygi MP, Thornock A, Zarraga G, Tam S, Szpyt J, Gassaway BM, Panov A, Parzen H, Fu S, Golbazi A, Maenpaa E, Stricker K, Guha Thakurta S, Zhang T, Rad R, Pan J, Nusinow DP, Paulo JA, Schweppe DK, Vaites LP, Harper JW, Gygi SP. 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. Epub 2021 May 06. PMID: 33961781; PMCID: PMC8165030.
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Cell. 2021 May 27;184(11):3022-3040.e28. doi: 10.1016/j.cell.2021.04.011. Epub 2021 May 06.

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

Cell

Edward L Huttlin, Raphael J Bruckner, Jose Navarrete-Perea, Joe R Cannon, Kurt Baltier, Fana Gebreab, Melanie P Gygi, Alexandra Thornock, Gabriela Zarraga, Stanley Tam, John Szpyt, Brandon M Gassaway, Alexandra Panov, Hannah Parzen, Sipei Fu, Arvene Golbazi, Eila Maenpaa, Keegan Stricker, Sanjukta Guha Thakurta, Tian Zhang, Ramin Rad, Joshua Pan, David P Nusinow, Joao A Paulo, Devin K Schweppe, Laura Pontano Vaites, J Wade Harper, Steven P Gygi

Affiliations

  1. Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: [email protected].
  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: [email protected].
  5. Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: [email protected].

PMID: 33961781 PMCID: PMC8165030 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.

Copyright © 2021 Elsevier Inc. All rights reserved.

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

Conflict of interest statement

Declaration of interests J.W.H. is a founder and scientific advisory board member of Caraway Therapeutics and a Founding Scientific Advisor for Interline Therapeutics.

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