Non-interacting proteins may resemble interacting proteins: prevalence and implications

Area of Science:

• Molecular Biology
• Structural Biology
• Systems Biology

Background:

• Most protein pairs do not form functional interactions under physiological conditions.
• Understanding the structural basis of protein interactions is crucial for cell biology.
• The potential for non-functional structural compatibility remains largely unexplored.

Purpose of the Study:

• To investigate structural compatibility among non-interacting protein pairs in Saccharomyces cerevisiae.
• To quantify the prevalence of structurally compatible, yet functionally non-interacting, protein pairs.
• To assess the potential impact of these compatible non-interactions on cellular protein-protein interaction networks.

Main Methods:

• Comparative analysis of 3D structures of non-interacting protein pairs against experimental complexes.
• Utilizing structural similarity metrics to identify compatible protein structures.
• Network analysis to evaluate the potential hazard posed by compatible non-interacting pairs.

Main Results:

• A significant proportion of non-interacting protein pairs exhibit structural similarity to known functional complexes.
• An estimated 8.7% of non-interacting protein pairs possess compatible structures.
• These compatible non-interactions are approximately 40 times more numerous than functional interactions.
• Network analysis indicates these interactions could be hazardous to the protein-protein interaction network.

Conclusions:

• A substantial number of protein pairs possess compatible structures despite lacking reported functional interactions.
• These structurally compatible non-interactions may represent a significant, previously uncharacterized component of cellular interactomes.
• The potential stability and physical interactor enrichment of these interactions suggest regulatory mechanisms are essential to prevent aberrant cellular activity.