Toxin structures as evolutionary tools: Using conserved 3D folds to study the evolution of rapidly evolving peptides

Area of Science:

• Structural Biology
• Evolutionary Biology
• Biochemistry

Background:

• Three-dimensional (3D) protein structures are widely used in evolutionary studies.
• The application of 3D structures to peptide evolution, particularly peptide toxins, is less explored.
• Disulfide-rich peptide folds, like the inhibitor cystine knot, are common in animal toxins.

Purpose of the Study:

• To highlight the utility of 3D structures in studying the molecular evolution of peptide toxins.
• To demonstrate how conserved 3D folds can aid in understanding peptide evolution.
• To extend these findings to other disulfide-constrained peptides.

Main Methods:

• Focus on analyzing conserved 3D protein folds.
• Application to animal toxins, specifically disulfide-rich folds.
• Utilizing structural information to infer evolutionary relationships.

Main Results:

• Conserved 3D folds can identify evolutionary links between peptides with low sequence identity.
• 3D structures facilitate the construction of accurate multiple sequence alignments.
• Structural insights enhance the understanding of evolutionary forces driving peptide evolution.

Conclusions:

• 3D structures are valuable tools for studying the molecular evolution of peptides, especially toxins.
• Conserved folds provide a framework for investigating the evolutionary origins and diversification of peptides.
• The approach is broadly applicable to disulfide-constrained peptides beyond toxins.