Repeatability of protein structural evolution following convergent gene fusions

Area of Science:

• Biochemistry
• Molecular Evolution
• Structural Biology

Background:

• Convergent evolution of proteins is key to understanding genetic adaptation.
• Local protein convergence (residue/domain) is known, but global structural convergence via inter-domain/molecular interactions is less understood.

Purpose of the Study:

• To investigate structural convergent evolution in fusion enzymes, specifically aldehyde dehydrogenases (ALDHs) and alcohol dehydrogenases (ADHs).
• To characterize a newly discovered enzyme clade, bifunctional dehydrogenase E (BdhE), and compare it to the known AdhE family.

Main Methods:

• Comparative analysis of enzyme structures and sequences.
• Cryo-electron microscopy to determine the quaternary structure of BdhE.
• Phylogenetic analysis to understand evolutionary relationships.

Main Results:

• Discovery of BdhE, an enzyme clade arising from independent gene fusion events, distinct from the AdhE family.
• BdhEs form donut-like homotetramers, while AdhEs form helical homopolymers.
• Despite low sequence identity (<30%), both enzymes exhibit similar dimeric structures through convergently evolved loop interactions, facilitating substrate channeling.

Conclusions:

• Convergent gene fusions have recurrently driven the evolution of substrate channeling to enhance the efficiency of two-step enzymatic reactions.
• This study reveals structural convergence at the inter-domain/molecular level, broadening our understanding of protein structural evolution patterns.