A large accessory protein interactome is rewired across environments.

Area of Science:

• Molecular Biology
• Systems Biology
• Biochemistry

Background:

• Protein-protein interactions (PPIs) are fundamental to cellular processes.
• Understanding the dynamic nature of PPI networks is crucial for comprehending cellular adaptation.
• Previous studies have often characterized PPIs under single conditions, potentially underestimating network complexity.

Purpose of the Study:

• To systematically map and quantify protein-protein interaction networks across diverse growth conditions in yeast.
• To identify and characterize 'immutable' and 'mutable' protein-protein interactions.
• To investigate the relationship between PPI dynamics and cellular adaptation.

Main Methods:

• Quantitative measurement of relative protein-protein interaction abundance for 1.6 million protein pairs in Saccharomyces cerevisiae.
• High-throughput screening across nine distinct growth conditions with replication.
• Analysis of protein co-expression, co-localization, and kinetic properties.

Main Results:

• Identified 13,764 pairwise PPIs, a threefold increase compared to single-condition studies.
• Discovered a small set of 'immutable' PPIs forming a core network and numerous 'mutable' PPIs within an accessory module.
• Mutable PPIs are associated with intrinsically disordered regions and environment-dependent binding, suggesting a role in adaptation.

Conclusions:

• Yeast protein interactomes are larger and more dynamic than previously recognized.
• Network remodeling, particularly in the accessory module, is critical for cellular adaptation.
• Environment-dependent protein associations are key to cellular plasticity.