dorsal/arxiv
View SchemaRobust protein-protein interactions in crowded cellular environments
| Authors | Eric Deeds, orr Ashenberg, Jaline Gerardine, Eugene Shakhnovich |
|---|---|
| Categories | |
| ArXiv ID | q-bio/0703060 |
| URL | https://arxiv.org/abs/q-bio/0703060 |
| DOI | 10.1073/pnas.0702766104 |
Abstract
The 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 to specific interaction possibilities. Here we address these questions 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, while 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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"abstract": "The capacity of proteins to interact specifically with one another underlies\nour conceptual understanding of how living systems function. Systems-level\nstudy of specificity in protein-protein interactions is complicated by the fact\nthat the cellular environment is crowded and heterogeneous; interaction pairs\nmay exist at low relative concentrations and thus be presented with many more\nopportunities for promiscuous interactions compared to specific interaction\npossibilities. Here we address these questions using a simple computational\nmodel that includes specifically designed interacting model proteins immersed\nin a mixture containing hundreds of different unrelated ones; all of them\nundergo simulated diffusion and interaction. We find that specific complexes\nare quite robust to interference from promiscuous interaction partners, only in\nthe range of temperatures Tdesign\u003eT\u003eTrand. At T\u003eTdesign specific complexes\nbecome unstable, while at T\u003cTrand formation of specific complexes is suppressed\nby promiscuous interactions. Specific interactions can form only if\nTdesign\u003eTrand. This condition requires an energy gap between binding energy in\na specific complex and set of binding energies between randomly associating\nproteins, providing a general physical constraint on evolutionary selection or\ndesign of specific interacting protein interfaces. This work has implications\nfor our understanding of how the protein repertoire functions and evolves\nwithin the context of cellular systems.",
"arxiv_id": "q-bio/0703060",
"authors": [
"Eric Deeds",
"orr Ashenberg",
"Jaline Gerardine",
"Eugene Shakhnovich"
],
"categories": [
"q-bio.BM",
"q-bio.MN"
],
"doi": "10.1073/pnas.0702766104",
"title": "Robust protein-protein interactions in crowded cellular environments",
"url": "https://arxiv.org/abs/q-bio/0703060"
},
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