Structural disorder promotes assembly of protein complexes

Hegyi, Hedi; Schad, Eva; Tompa, Peter
January 2007
BMC Structural Biology;2007, Vol. 7, p65
Academic Journal
Background: The idea that the assembly of protein complexes is linked with protein disorder has been inferred from a few large complexes, such as the viral capsid or bacterial flagellar system, only. The relationship, which suggests that larger complexes have more disorder, has never been systematically tested. The recent high-throughput analyses of protein-protein interactions and protein complexes in the cell generated data that enable to address this issue by bioinformatic means. Results: In this work we predicted structural disorder for both E. coli and S. cerevisiae, and correlated it with the size of complexes. Using IUPred to predict the disorder for each complex, we found a statistically significant correlation between disorder and the number of proteins assembled into complexes. The distribution of disorder has a median value of 10% in yeast for complexes of 2-4 components (6% in E. coli), but 18% for complexes in the size range of 11-100 proteins (12% in E. coli). The level of disorder as assessed for regions longer than 30 consecutive disordered residues shows an even stronger division between small and large complexes (median values about 4% for complexes of 2-4 components, but 12% for complexes of 11-100 components in yeast). The predicted correlation is also supported by experimental evidence, by observing the structural disorder in protein components of complexes that can be found in the Protein Data Bank (median values 1. 5% for complexes of 2-4 components, and 9.6% for complexes of 11-100 components in yeast). Further analysis shows that this correlation is not directly linked with the increased disorder in hub proteins, but reflects a genuine systemic property of the proteins that make up the complexes. Conclusion: Overall, it is suggested and discussed that the assembly of protein-protein complexes is enabled and probably promoted by protein disorder.


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