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

Autor: Huttlin EL; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: edward_huttlin@hms.harvard.edu., Bruckner RJ; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA., Navarrete-Perea J; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA., Cannon JR; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA., Baltier K; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA., Gebreab F; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA., Gygi MP; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA., Thornock A; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA., Zarraga G; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA., Tam S; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA., Szpyt J; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA., Gassaway BM; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA., Panov A; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA., Parzen H; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA., Fu S; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA., Golbazi A; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA., Maenpaa E; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA., Stricker K; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA., Guha Thakurta S; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA., Zhang T; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA., Rad R; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA., Pan J; Broad Institute, Cambridge, MA 02142, USA., Nusinow DP; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA., Paulo JA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA., Schweppe DK; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA., Vaites LP; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA., Harper JW; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: wade_harper@hms.harvard.edu., Gygi SP; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: steven_gygi@hms.harvard.edu.
Jazyk: angličtina
Zdroj: Cell [Cell] 2021 May 27; Vol. 184 (11), pp. 3022-3040.e28. Date of Electronic Publication: 2021 May 06.
DOI: 10.1016/j.cell.2021.04.011
Abstrakt: 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.
Competing Interests: 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.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE