To characterize how protein-protein interaction (PPI) networks change, we quantified the relative PPI abundance of 1.6 million protein pairs in the yeast Saccharomyces cerevisiae across 9 growth conditions, with replication, for a total of 44 million measurements. Our multi-condition screen identified 13,764 pairwise PPIs, a 3-fold increase over PPIs identified in one condition. A few 'immutable' PPIs are present across all conditions, while most 'mutable' PPIs are rarely observed. Immutable PPIs aggregate into highly connected 'core' network modules, with most network remodeling occurring within a loosely connected 'accessory' module. Mutable PPIs are less likely to co-express, co-localize, and be explained by simple mass action kinetics, and more likely to contain proteins with intrinsically disordered regions, implying that environment-dependent association and binding is critical to cellular adaptation. Our results show that protein interactomes are larger than previously thought and contain highly dynamic regions that reorganize to drive or respond to cellular changes.
Raw barcode sequencing data are available from the NIH Sequence Read Archive as accession PRJNA630095 (https://trace.ncbi.nlm.nih.gov/Traces/study/?acc=SRP259652). Barcode sequences, counts, fitness values, and PPI calls are available in the Supplementary Tables (https://osf.io/jmhrb/). Additional data to make figures are available in Mendeley data (https://data.mendeley.com/datasets/9ygwhk5cs3/2) and Open Science Framework (https://osf.io/7yt59/) as detailed in code repository README files. Analysis scripts are written in R and Python. All code used to analyze data, perform statistical analyses, and generate figures is available at Github (https://github.com/sashaflevy/PPiSeq).
Protein-protein interaction network rewiring across environmentsMendelay Data, DOI: 10.17632/9ygwhk5cs3.2.
Protein-protein interaction network dynamics across environments by DNA barcode sequencingNIH Sequence Read Archive, accession PRJNA630095.
- Sasha F Levy
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Christian R Landry, Université Laval, Canada
© 2020, Liu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.