Evolution shapes interaction patterns for epistasis and specific protein binding in a two-component signaling system.

Area of Science:

• Molecular Biology
• Evolutionary Biology
• Biophysics

Background:

• Protein sequence, structure, and function are intricately linked through amino acid interaction patterns.
• Understanding how evolutionary forces shape these patterns, particularly long-range epistasis and binding specificity, is a key challenge.
• Two-component signaling (TCS) systems provide a model for studying these evolutionary dynamics.

Purpose of the Study:

• To investigate how evolutionary forces shape interaction patterns in TCS systems.
• To elucidate the mechanisms underlying long-range epistasis and binding specificity.
• To differentiate between family-wide conserved and structure-specific interaction patterns.

Main Methods:

• Combined family-wide evolutionary analysis of homologous sequences.
• Employed structure-oriented evolution simulations for TCS systems.
• Analyzed coupling conservation patterns and their distribution.

Main Results:

• Coupling conservation between amino acid positions follows a power-law-like distribution.
• Highly conserved positions are sparse but concentrated on binding surfaces and in the hydrophobic core.
• Structure-specific patterns reveal optimization of local frustrations for partner adaptation.
• Binding specificity is modulated by direct interactions and long-range epistasis.

Conclusions:

• Evolution sculpts protein interaction patterns at both family-wide and structure-specific levels.
• These evolutionary processes are crucial for adapting binding specificity in TCS systems.
• The study provides insights into the interplay between sequence variation, structure, and function evolution.