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Mol Syst Biol. 2017 Jul 13;13(7):934. doi: 10.15252/msb.20177532.

Quantitative analysis of protein interaction network dynamics in yeast.

Celaj A1,2,3, Schlecht U4,5, Smith JD4,6, Xu W4, Suresh S4,5, Miranda M4,5, Aparicio AM4,5, Proctor M4,5, Davis RW4,5,6, Roth FP7,2,3,8,9, St Onge RP10,5.

Author information

1
Departments of Molecular Genetics and Computer Science, University of Toronto, Toronto, ON, Canada.
2
Donnelly Centre, University of Toronto, Toronto, ON, Canada.
3
Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.
4
Stanford Genome Technology Center, Stanford University, Palo Alto, CA, USA.
5
Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, USA.
6
Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
7
Departments of Molecular Genetics and Computer Science, University of Toronto, Toronto, ON, Canada fritz.roth@utoronto.ca bstonge@stanford.edu.
8
Canadian Institute for Advanced Research, Toronto, ON, Canada.
9
Center for Cancer Systems Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
10
Stanford Genome Technology Center, Stanford University, Palo Alto, CA, USA fritz.roth@utoronto.ca bstonge@stanford.edu.

Abstract

Many cellular functions are mediated by protein-protein interaction networks, which are environment dependent. However, systematic measurement of interactions in diverse environments is required to better understand the relative importance of different mechanisms underlying network dynamics. To investigate environment-dependent protein complex dynamics, we used a DNA-barcode-based multiplexed protein interaction assay in Saccharomyces cerevisiae to measure in vivo abundance of 1,379 binary protein complexes under 14 environments. Many binary complexes (55%) were environment dependent, especially those involving transmembrane transporters. We observed many concerted changes around highly connected proteins, and overall network dynamics suggested that "concerted" protein-centered changes are prevalent. Under a diauxic shift in carbon source from glucose to ethanol, a mass-action-based model using relative mRNA levels explained an estimated 47% of the observed variance in binary complex abundance and predicted the direction of concerted binary complex changes with 88% accuracy. Thus, we provide a resource of yeast protein interaction measurements across diverse environments and illustrate the value of this resource in revealing mechanisms of network dynamics.

KEYWORDS:

environmental response; mRNA expression; network dynamics; protein complementation assay; protein–protein interactions

PMID:
28705884
PMCID:
PMC5527849
DOI:
10.15252/msb.20177532
[Indexed for MEDLINE]
Free PMC Article

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