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

Research output: Contribution to journalJournal articleResearchpeer-review

  • Marco Y Hein
  • Nina C Hubner
  • Ina Poser
  • Jürgen Cox
  • Nagarjuna Nagaraj
  • Yusuke Toyoda
  • Igor A Gak
  • Ina Weisswange
  • Jörg Mansfeld
  • Frank Buchholz
  • Anthony A Hyman
  • Matthias Mann

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.

Original languageEnglish
Issue number3
Pages (from-to)712-23
Number of pages12
Publication statusPublished - 22 Oct 2015
Externally publishedYes

Bibliographical note

Copyright © 2015 Elsevier Inc. All rights reserved.

    Research areas

  • Cell Line, Chromosomes, Artificial, Bacterial/genetics, Humans, Protein Interaction Mapping, Proteomics/methods

ID: 246723804