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. 2015 Oct 22;163(3):712-23.
doi: 10.1016/j.cell.2015.09.053. Epub 2015 Oct 22.

A human interactome in three quantitative dimensions organized by stoichiometries and abundances

Marco Y Hein  1 , Nina C Hubner  1 , Ina Poser  2 , Jürgen Cox  1 , Nagarjuna Nagaraj  1 , Yusuke Toyoda  2 , Igor A Gak  3 , Ina Weisswange  4 , Jörg Mansfeld  3 , Frank Buchholz  5 , Anthony A Hyman  6 , Matthias Mann  7
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Free article

A human interactome in three quantitative dimensions organized by stoichiometries and abundances

Marco Y Hein et al. Cell. .
Free article

Abstract

The organization of a cell emerges from the interactions in protein networks. The interactome is critically dependent on the strengths of interactions and the cellular abundances of the connected proteins, both of which span orders of magnitude. However, these aspects have not yet been analyzed globally. Here, we have generated a library of HeLa cell lines expressing 1,125 GFP-tagged proteins under near-endogenous control, which we used as input for a next-generation interaction survey. Using quantitative proteomics, we detect specific interactions, estimate interaction stoichiometries, and measure cellular abundances of interacting proteins. These three quantitative dimensions reveal that the protein network is dominated by weak, substoichiometric interactions that play a pivotal role in defining network topology. The minority of stable complexes can be identified by their unique stoichiometry signature. This study provides a rich interaction dataset connecting thousands of proteins and introduces a framework for quantitative network analysis.

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Comment in

  • Nat Methods. 2016 Jan;13(1):14
  • Proteomics: Strength in numbers.
    Minton K. Minton K. Nat Rev Mol Cell Biol. 2015 Dec;16(12):702-3. doi: 10.1038/nrm4086. Epub 2015 Nov 4. Nat Rev Mol Cell Biol. 2015. PMID: 26530387 No abstract available.
  • The power of 'weak' interactions.
    de Souza N. de Souza N. Nat Methods. 2016 Jan;13(1):14. doi: 10.1038/nmeth.3725. Nat Methods. 2016. PMID: 27110627 No abstract available.

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