Title
Evolutionary Capacitance and Control of Protein Stability in Protein-Protein Interaction Networks.
Abstract
In addition to their biological function, protein complexes reduce the exposure of the constituent proteins to the risk of undesired oligomerization by reducing the concentration of the free monomeric state. We interpret this reduced risk as a stabilization of the functional state of the protein. We estimate that protein-protein interactions can account for similar to 2-4 k(B)T of additional stabilization; a substantial contribution to intrinsic stability. We hypothesize that proteins in the interaction network act as evolutionary capacitors which allows their binding partners to explore regions of the sequence space which correspond to less stable proteins. In the interaction network of baker's yeast, we find that statistically proteins that receive higher energetic benefits from the interaction network are more likely to misfold. A simplified fitness landscape wherein the fitness of an organism is inversely proportional to the total concentration of unfolded proteins provides an evolutionary justification for the proposed trends. We conclude by outlining clear biophysical experiments to test our predictions.
Year
DOI
Venue
2013
10.1371/journal.pcbi.1003023
PLOS COMPUTATIONAL BIOLOGY
Field
DocType
Volume
Protein folding,Fitness landscape,Protein–protein interaction,Biology,Interaction network,Fungal protein,Evolutionary capacitance,Chaperone (protein),Bioinformatics,Genetics,Protein structure
Journal
9
Issue
ISSN
Citations 
4
1553-734X
1
PageRank 
References 
Authors
0.36
5
2
Name
Order
Citations
PageRank
Purushottam D. Dixit131.45
Sergei Maslov21337.69