Functional evolution of two subtly different (similar) folds

Area of Science:

• Structural biology
• Protein folding
• Bioinformatics

Background:

• Protein function is determined by its 3D structure.
• Protein structural classification describes folding patterns.
• Functional properties of protein folds remain understudied.

Purpose of the Study:

• To analyze and differentiate two beta-barrel protein folds with similar structures but different topologies.
• To investigate the relationship between fold topology, sequence diversity, loop variability, and protein function.
• To explore the evolutionary origins of these protein folds.

Main Methods:

• Comparative analysis of two beta-barrel protein folds (SH3-fold and OB-fold).
• Examination of sequence homology and loop variability.
• Functional characterization based on structural topology.

Main Results:

• Identified two distinct beta-barrel folds: SH3-fold and OB-fold, differing in topology despite superficial similarity.
• Found no significant sequence homology between analyzed proteins.
• Demonstrated that sequence diversity and loop variability are crucial for diverse binding functions.

Conclusions:

• Oligonucleotide/oligosaccharide-binding (OB) fold proteins are primarily involved in DNA/RNA or sugar binding.
• Src homology 3 (SH3) domain-like proteins exhibit versatile ligand binding through loop modulation.
• Investigated the potential role of DNA shuffling in the evolution of these two protein folds.