Structural disorder promotes assembly of protein complexes.

Area of Science:

• Molecular Biology
• Biophysics
• Bioinformatics

Background:

• The link between protein disorder and complex assembly was previously inferred from limited examples.
• A systematic investigation into this relationship, especially concerning complex size, was lacking.

Purpose of the Study:

• To systematically test the hypothesis that larger protein complexes exhibit increased intrinsic disorder.
• To investigate the correlation between the size of protein complexes and their predicted structural disorder using bioinformatic approaches.

Main Methods:

• Prediction of structural disorder for proteins within complexes in E. coli and S. cerevisiae using IUPred.
• Correlation analysis between predicted disorder levels and the number of protein components in complexes.
• Validation using experimental data from the Protein Data Bank (PDB).

Main Results:

• A statistically significant positive correlation was found between protein complex size and disorder.
• Larger complexes (11-100 proteins) showed higher median disorder (18% in yeast, 12% in E. coli) compared to smaller ones (2-4 proteins; 10% in yeast, 6% in E. coli).
• Experimental data from PDB supported these findings, with larger complexes exhibiting greater disorder.

Conclusions:

• Protein disorder is a systemic property that facilitates the assembly of protein-protein complexes.
• The findings suggest that intrinsic protein disorder plays a crucial role in enabling and promoting the formation of larger protein assemblies.