Department of Biochemistry, Stony Brook University, Stony Brook, United States; Laufer Center for Physical and Quantitative Biology, Stony Brook University, Stony Brook, United States
Joint Initiative for Metrology in Biology, Stanford, United States; Department of Genetics, Stanford University, Stanford, United States
Fangfei Li
Laufer Center for Physical and Quantitative Biology, Stony Brook University, Stony Brook, United States; Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, United States
Xianan Liu
Department of Biochemistry, Stony Brook University, Stony Brook, United States; Laufer Center for Physical and Quantitative Biology, Stony Brook University, Stony Brook, United States
Department of Biochemistry, Stony Brook University, Stony Brook, United States; Laufer Center for Physical and Quantitative Biology, Stony Brook University, Stony Brook, United States; Joint Initiative for Metrology in Biology, Stanford, United States; Department of Genetics, Stanford University, Stanford, United States; Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, United States; SLAC National Accelerator Laboratory, Menlo Park, United States
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 nine growth conditions, with replication, for a total of 44 million measurements. Our multi-condition screen identified 13,764 pairwise PPIs, a threefold 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.