Robust protein protein interactions in crowded cellular environments
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Deeds, E. J.
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CitationDeeds, E. J., O. Ashenberg, J. Gerardin, and E. I. Shakhnovich. 2007. “Robust Protein Protein Interactions in Crowded Cellular Environments.” Proceedings of the National Academy of Sciences 104 (38) (September 11): 14952–14957. doi:10.1073/pnas.0702766104.
AbstractThe capacity of proteins to interact specifically with one another underlies our conceptual understanding of how living systems function. Systems-level study of specificity in protein–protein interactions is complicated by the fact that the cellular environment is crowded and heterogeneous; interaction pairs may exist at low relative concentrations and thus be presented with many more opportunities for promiscuous interactions compared with specific interaction possibilities. Here we address these questions by using a simple computational model that includes specifically designed interacting model proteins immersed in a mixture containing hundreds of different unrelated ones; all of them undergo simulated diffusion and interaction. We find that specific complexes are quite robust to interference from promiscuous interaction partners only in the range of temperatures Tdesign > T > Trand. At T > Tdesign, specific complexes become unstable, whereas at T < Trand, formation of specific complexes is suppressed by promiscuous interactions. Specific interactions can form only if Tdesign > Trand. This condition requires an energy gap between binding energy in a specific complex and set of binding energies between randomly associating proteins, providing a general physical constraint on evolutionary selection or design of specific interacting protein interfaces. This work has implications for our understanding of how the protein repertoire functions and evolves within the context of cellular systems.
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