Evolutionary Capacitance and Control of Protein Stability in Protein-Protein Interaction Networks

University of Wyoming, United States of America
PLoS Computational Biology (Impact Factor: 4.62). 04/2013; 9(4):e1003023. DOI: 10.1371/journal.pcbi.1003023
Source: PubMed


Author Summary
The folded form of proteins is only marginally stable in vivo and constantly faces the risk of aggregation, unfolding/misfolding, and other aberrant interactions. For most proteins, the folded form is also the functionally relevant one and forces of natural selection strongly modulate its stability. In vivo, proteins interact with each other on a genome-wide scale. Usually, the interaction of a protein and its binding partners requires both the proteins to be in the folded form and as a result, the interactions tend to shift the population of a protein towards the folded form. Consequently, protein-protein interactions interfere with the evolution of protein stability. Here, we present empirical evidence and theoretical justification for proteins' ability to stabilize the folded form of their interaction partners and allow them to explore the region of the sequence space that corresponds to proteins with less stable structure. We argue that the ‘evolutionary capacitance’ – previously thought to be a property of the chaperone HSP90, a special class of proteins – is a property of all proteins, albeit to a different degree.

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