Computational Assessment of Bacterial Protein Structures Indicates a Selection Against Aggregation

Area of Science:

• Biochemistry
• Molecular Biology
• Evolutionary Biology

Background:

• Protein aggregation compromises cellular function and fitness by forming non-productive or toxic assemblies.
• Computational analyses indicate that preventing aggregation during misfolding is crucial for protein sequence evolution.
• Proteins exist primarily in a folded state, suggesting structural evolution may also play a role in minimizing aggregation risk.

Purpose of the Study:

• To investigate whether protein structures have evolved to minimize aggregation propensity in their natural environments.
• To explore the relationship between structural aggregation propensity and various protein properties in Escherichia coli.

Main Methods:

• Utilized the AGGRESCAN3D structure-based approach to predict protein aggregation propensity.
• Analyzed aggregation propensity for over 600 proteins from Escherichia coli.
• Correlated structural aggregation propensity with protein abundance, length, essentiality, subcellular location, and quaternary structure.

Main Results:

• Structural aggregation propensity of globular proteins in Escherichia coli is linked to their abundance, length, essentiality, subcellular location, and quaternary structure.
• Demonstrated a connection between protein structure and aggregation risk within the bacterial proteome.

Conclusions:

• The avoidance of protein aggregation has likely contributed to shaping the structural characteristics of proteins in bacterial cells.
• Evolutionary pressures to prevent aggregation influence protein structure, thereby maintaining cellular fitness.