Cellular location shapes quaternary structure of enzymes

Area of Science:

• Biochemistry
• Evolutionary Biology
• Structural Biology

Background:

• The evolutionary drivers of protein complex formation, particularly in homomers, remain unclear.
• Quaternary structure evolution may be influenced by neutral processes rather than solely adaptive advantages.

Purpose of the Study:

• To investigate the factors influencing protein oligomerization, focusing on enzyme evolution in specific cellular contexts.
• To differentiate between adaptive and neutral evolution models for quaternary structure acquisition.

Main Methods:

• Analysis of enzyme evolution across different cellular compartments (extracellular vs. cytoplasmic).
• Comparative analysis of protein orthogroups to assess quaternary structure changes.
• Evaluation of evolutionary patterns against constructive neutral evolution predictions.

Main Results:

• Enzymes in extracellular environments are predominantly monomers, while cytoplasmic enzymes are often homomers.
• Quaternary structure evolution aligns with constructive neutral evolution: gain is easier than loss.
• Extracellular monomers typically evolved from ancestral monomers without interface loss.

Conclusions:

• Protein oligomerization is highly context-dependent, influenced by the cellular environment.
• Environmental factors like macromolecular crowding and homeostasis maintenance play significant roles in interface evolution.
• Adaptation of quaternary structure may be driven by environmental properties over intrinsic biochemical function.