June 2012

The evolution of unstructured protein interactions

Fig. 1 from Mosca et al article in MCP prepublished on March 2, 2012: The role of structural disorder in the rewiring of protein interactions through evolution, DOI 10.1074/mcp.M111.014969

The lock-and-key hypothesis of protein structural biology was held as dogma last century until examples started to crop up of proteins with flexible structures that could not be analyzed by conventional X-ray crystallography. In the past 15 years, the existence of proteins that don’t have any definite structure has been established. In a recent Molecular & Cellular Proteomics paper, a trio of European researchers analyzed the role of intrinsically disordered proteins in the evolution of interaction networks in three model organisms (1). “We and others noticed that there is a significant presence of unstructured proteins in interaction networks,” says Patrick Aloy at the Institute for Research in Biomedicine and the Catalan Institution for Research and Advanced Studies. He added that he and his colleagues wanted to understand “the role played by these proteins in the evolution of protein interaction networks.”

The researchers compared the molecular interaction networks in human, fly and yeast and discovered that, despite their abundance, interactions involving disordered proteins were less conserved than those that included structured proteins. “Despite being very abundant, protein interactions involving at least one unstructured protein are much less conserved than one would expect by chance,” says Aloy. He says that their results support the hypothesis that maintaining disordered proteins “gives a clear evolutionary advantage — it facilitates the change of interaction partners during evolution.” Aloy says his group is now investigating “the structural and functional effect of disease-causing mutations that occur in unstructured regions” to see if there are any biomedical applications.

  1. 1. Mosca, R. et al. Mol. Cell. Prot. DOI: 10.1074/mcp.M111.014969


Raj_MukhopadhyayRajendrani Mukhopadhyay (rmukhopadhyay@asbmb.org) is the senior science writer for ASBMB Today and the technical editor for The Journal of Biological Chemistry. Follow her on Twitter at @rajmukhop.

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