Functional determinants of protein assembly into homomeric complexes

Area of Science:

• Biochemistry and Structural Biology
• Evolutionary Biology
• Bioinformatics

Background:

• Proteins often form homomeric complexes, with most exhibiting symmetry.
• The functional advantages of homomerization are often assumed but lack systematic analysis.
• Understanding the relationship between homomer structure and biological function is crucial.

Purpose of the Study:

• To investigate the association between different types of protein homomer symmetries and specific biological functions.
• To explore the physical and geometrical basis for these structure-function relationships.
• To provide insights into protein evolution and quaternary structure prediction.

Main Methods:

• Analysis of large datasets of experimentally determined protein structures.
• Integration of structural data with functional annotations.
• Statistical analysis of homomer symmetry groups and associated functions.

Main Results:

• Homomers from different symmetry groups are significantly enriched in distinct biological functions.
• Physical and geometrical explanations link symmetry to substrate recognition and environmental adaptation.
• Metabolic enzymes frequently form dihedral complexes, associated with allosteric regulation.

Conclusions:

• A clear relationship exists between protein homomer symmetry and biological function.
• Dihedral symmetry facilitates efficient conformational changes for allosteric regulation in metabolic enzymes.
• Findings have implications for understanding protein evolution and predicting protein function and quaternary structure.