A human interactome in three quantitative dimensions organized by stoichiometries and abundances.
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.
Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
Marco Y
MY
Hein
Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
Nina C
NC
Hubner
Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
Ina
I
Poser
Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
Jürgen
J
Cox
Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
Nagarjuna
N
Nagaraj
Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
Yusuke
Y
Toyoda
Cell Cycle, Biotechnology Center, TU Dresden, 01307 Dresden, Germany.
Igor A
IA
Gak
Medical Systems Biology, UCC, Medical Faculty Carl Gustav Carus, TU Dresden, 01307 Dresden, Germany; Eupheria Biotech GmbH, 01307 Dresden, Germany.
Ina
I
Weisswange
Cell Cycle, Biotechnology Center, TU Dresden, 01307 Dresden, Germany.
Jörg
J
Mansfeld
Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany; Medical Systems Biology, UCC, Medical Faculty Carl Gustav Carus, TU Dresden, 01307 Dresden, Germany.
Frank
F
Buchholz
Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany. Electronic address: hyman@mpi-cbg.de.
Anthony A
AA
Hyman
Max Planck Institute of Biochemistry, 82152 Martinsried, Germany. Electronic address: mmann@biochem.mpg.de.
Matthias
M
Mann
D002460:Cell Line; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D006801:Humans; D025941:Protein Interaction Mapping; D040901:Proteomics / Q000379:methods*