Binding interface change and cryptic variation in the evolution of protein-protein interactions

Area of Science:

• Molecular Biology
• Evolutionary Biology
• Biochemistry

Background:

• Protein-protein interactions are fundamental to biological processes.
• Understanding the evolution of molecular interactions, especially binding specificity, is crucial for deciphering functional evolution.
• Protein interaction interfaces are complex, with residues influencing specificity, affinity, structural integrity, and solubility.

Purpose of the Study:

• To investigate the relationship between the composition of protein interaction interfaces and the evolution of binding specificity.
• To analyze how amino acid changes in protein interfaces correlate with alterations in binding specificity over evolutionary time.

Main Methods:

• Utilized paralogous pairs of yeast proteins to study interface evolution.
• Correlated amino acid sequence divergence within interfaces with changes in binding specificity post-gene duplication.

Main Results:

• Observed a weak correlation between changes in protein interface regions and alterations in binding specificity.
• Demonstrated that numerous amino acid variants within interfaces are functionally equivalent, having no impact on binding specificity.

Conclusions:

• Functionally equivalent changes in protein interfaces can generate cryptic variation.
• This cryptic variation provides a reservoir for evolutionary plasticity, enabling functional innovation and coevolution of protein interaction networks.