dorsal/arxiv
View SchemaNonlinear Protein Degradation and the Function of Genetic Circuits
| Authors | Nicolas E. Buchler, Ulrich Gerland, Terence Hwa |
|---|---|
| Categories | |
| ArXiv ID | q-bio/0501002 |
| URL | https://arxiv.org/abs/q-bio/0501002 |
| DOI | 10.1073/pnas.0409553102 |
Abstract
The functions of most genetic circuits require sufficient degrees of cooperativity in the circuit components. While mechanisms of cooperativity have been studied most extensively in the context of transcriptional initiation control, cooperativity from other processes involved in the operation of the circuits can also play important roles. In this study, we examine a simple kinetic source of cooperativity stemming from the nonlinear degradation of multimeric proteins. Ample experimental evidence suggests that protein subunits can degrade less rapidly when associated in multimeric complexes, an effect we refer to as cooperative stability. For dimeric transcription factors, this effect leads to a concentration-dependence in the degradation rate because monomers, which are predominant at low concentrations, will be more rapidly degraded. Thus cooperative stability can effectively widen the accessible range of protein levels in vivo. Through theoretical analysis of two exemplary genetic circuits in bacteria, we show that such an increased range is important for the robust operation of genetic circuits as well as their evolvability. Our calculations demonstrate that a few-fold difference between the degradation rate of monomers and dimers can already enhance the function of these circuits substantially. These results suggest that cooperative stability needs to be considered explicitly and characterized quantitatively in any systematic experimental or theoretical study of gene circuits.
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"abstract": "The functions of most genetic circuits require sufficient degrees of\ncooperativity in the circuit components. While mechanisms of cooperativity have\nbeen studied most extensively in the context of transcriptional initiation\ncontrol, cooperativity from other processes involved in the operation of the\ncircuits can also play important roles. In this study, we examine a simple\nkinetic source of cooperativity stemming from the nonlinear degradation of\nmultimeric proteins. Ample experimental evidence suggests that protein subunits\ncan degrade less rapidly when associated in multimeric complexes, an effect we\nrefer to as cooperative stability. For dimeric transcription factors, this\neffect leads to a concentration-dependence in the degradation rate because\nmonomers, which are predominant at low concentrations, will be more rapidly\ndegraded. Thus cooperative stability can effectively widen the accessible range\nof protein levels in vivo. Through theoretical analysis of two exemplary\ngenetic circuits in bacteria, we show that such an increased range is important\nfor the robust operation of genetic circuits as well as their evolvability. Our\ncalculations demonstrate that a few-fold difference between the degradation\nrate of monomers and dimers can already enhance the function of these circuits\nsubstantially. These results suggest that cooperative stability needs to be\nconsidered explicitly and characterized quantitatively in any systematic\nexperimental or theoretical study of gene circuits.",
"arxiv_id": "q-bio/0501002",
"authors": [
"Nicolas E. Buchler",
"Ulrich Gerland",
"Terence Hwa"
],
"categories": [
"q-bio.MN",
"q-bio.BM"
],
"doi": "10.1073/pnas.0409553102",
"title": "Nonlinear Protein Degradation and the Function of Genetic Circuits",
"url": "https://arxiv.org/abs/q-bio/0501002"
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