Co-evolution of proteins with their interaction partners

Area of Science:

• Molecular Biology
• Evolutionary Biology
• Biochemistry

Background:

• Ligand-receptor co-evolution is crucial for cellular signaling pathway diversification.
• Assessing binding specificity evolution from sequence data alone is challenging.

Purpose of the Study:

• To develop a quantitative method for measuring protein co-evolution.
• To establish an upper bound for the co-evolution of protein domains and their binding partners.
• To apply this method to ligand-receptor systems, using chemokines as a model.

Main Methods:

• Utilized phosphoglycerate kinase (PGK) as a model system due to its two co-evolving domains forming the active site.
• Constructed phylogenetic trees from multiple sequence alignments of PGK's N-terminal and C-terminal domains.
• Calculated a correlation coefficient between these phylogenetic trees to quantify domain co-evolution.
• Extended the analysis to chemokine ligands and their G-protein coupled receptors.

Main Results:

• The correlation coefficient for PGK domains was 0.79, indicating a high degree of co-evolution and establishing an upper bound.
• The correlation coefficient for chemokine ligand and receptor trees was 0.57.
• Demonstrated that chemokine subfamilies co-evolve with matching receptor subfamilies.

Conclusions:

• The developed method provides a quantitative measure for protein co-evolution.
• The findings establish an upper bound for protein domain co-evolution.
• The approach aids in identifying ligands for orphan chemokine receptors and can be applied to other ligand-receptor systems.