Architectures and functional coverage of protein-protein interfaces

Area of Science:

• Structural Biology
• Bioinformatics
• Computational Biology

Background:

• Cellular functions rely on a finite repertoire of protein folds.
• A similar principle may apply to protein-protein interactions, suggesting a limited number of interface architectures govern functional diversity.

Purpose of the Study:

• To identify and categorize unique protein-protein interface architectures.
• To analyze the growth trends of interface architectures and functional coverage over time.
• To compare current findings with existing datasets of protein interfaces.

Main Methods:

• Clustering of 8205 protein-protein interfaces to define unique architectures.
• Comparative analysis of the current dataset with historical protein-protein interface data.
• Construction of functional interaction networks from interfaces to assess functional coverage.

Main Results:

• A dataset of 8205 distinct protein-protein interface architectures was established.
• The number of biological and crystal interfaces has significantly increased relative to Protein Data Bank entries.
• The count of unique interface architectures is growing faster than protein folds and has not yet plateaued; functional coverage also shows a steady increase.

Conclusions:

• A limited set of protein-protein interface architectures underlies the diverse functional landscape of cells.
• Certain interface architectures are more prevalent and favored, including those also found in single protein chains.
• The continuous growth in interface architectures suggests ongoing discovery and evolving understanding of protein interactions.