An evolutionarily structured universe of protein architecture

Area of Science:

• Biochemistry
• Evolutionary Biology
• Structural Biology

Background:

• Protein structural diversity is finite, containing embedded evolutionary histories.
• Understanding protein fold evolution is key to deciphering proteome diversification.

Purpose of the Study:

• To reconstruct phylogenies of protein architectures and proteomes using cladistic principles.
• To investigate the evolutionary order of protein structural classes and their transformation pathways.
• To explore the link between protein structure and enzymatic function.

Main Methods:

• Cladistic analysis of protein fold usage and sharing.
• Reconstruction of rooted phylogenies for proteomes and protein architectures.
• Analysis of structural class emergence and transformation pathways.
• Tracing enzymatic functions associated with protein folds.

Main Results:

• Proteome phylogenies suggest Eucarya rooted the tree, with Bacteria and Archaea as sister groups, implying early eukaryotic-like organization.
• The alpha/beta class was the first globular protein structural class to appear.
• Ancestral folds often featured barrels or interleaved sheets/helices, with derived structures like polyhedral folds and beta-prisms also identified.
• Transformation pathways show favored outcomes, such as increased curl and stagger in beta-barrels, and an alpha-to-beta structural change tendency.
• A general link exists between protein structure and enzymatic function.

Conclusions:

• Protein evolution follows defined architectural pathways, with early structural classes established early in life's history.
• The study provides insights into the deep evolutionary history of life and the fundamental relationship between protein structure and function.