Limits...
Effects of multimerization on the temporal variability of protein complex abundance.

Häkkinen A, Tran H, Yli-Harja O, Ingalls B, Ribeiro AS - BMC Syst Biol (2013)

Bottom Line: We show that, although multimerization increases noise by reducing the mean number of functional complexes it can reduce noise in comparison with a monomer, when abundance of the functional proteins are comparable.Alternatively, reduction in noise occurs if both monomeric and multimeric forms of the protein are functional.Moreover, we find that multimerization either increases the response time to external signals or decreases the correlation between number of functional complexes and protein production kinetics.

View Article: PubMed Central - HTML - PubMed

ABSTRACT
We explore whether the process of multimerization can be used as a means to regulate noise in the abundance of functional protein complexes. Additionally, we analyze how this process affects the mean level of these functional units, response time of a gene, and temporal correlation between the numbers of expressed proteins and of the functional multimers. We show that, although multimerization increases noise by reducing the mean number of functional complexes it can reduce noise in comparison with a monomer, when abundance of the functional proteins are comparable. Alternatively, reduction in noise occurs if both monomeric and multimeric forms of the protein are functional. Moreover, we find that multimerization either increases the response time to external signals or decreases the correlation between number of functional complexes and protein production kinetics. Finally, we show that the results are in agreement with recent genome-wide assessments of cell-to-cell variability in protein numbers and of multimerization in essential and non-essential genes in Escherichia coli, and that the effects of multimerization are tangible at the level of genetic circuits.

Show MeSH

Related in: MedlinePlus

Change in mean switching time of toggle switch due to multimerization. Mean switching time of a toggle switch as a function of the inverse repression strength C, where the genetic interactions are implement with different orders of homomers, as a function of disassociation strength of repression.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3750523&req=5

Figure 8: Change in mean switching time of toggle switch due to multimerization. Mean switching time of a toggle switch as a function of the inverse repression strength C, where the genetic interactions are implement with different orders of homomers, as a function of disassociation strength of repression.

Mentions: The parameters used in the models were: RNA degradation rate dM = 6 dP, expected transcript number kM N−1dM−1 = 5, transcription kinetics shape αM = 1, expected number of protein per RNA kP dP−1 = 5, and disassociation of repression K = C kM N−1 dM −1 kP dP−1, where C was varied in the range [10−4, 104] with approximately logarithmic spacing (i.e. {a 10b/ a ∈ {1, 2, 3, ⋯ , 9}, b ∈ {−4, −3, −2, ⋯ , 4}}). The gene expression parameters are in agreement with live cell measurements in E. coli [6]. The switch's state was sampled with intervals of 1/30 time units, the simulations provided 106 samples. The mean switching time as a function of the inverse of the repression strength C is shown in Figure 8.


Effects of multimerization on the temporal variability of protein complex abundance.

Häkkinen A, Tran H, Yli-Harja O, Ingalls B, Ribeiro AS - BMC Syst Biol (2013)

Change in mean switching time of toggle switch due to multimerization. Mean switching time of a toggle switch as a function of the inverse repression strength C, where the genetic interactions are implement with different orders of homomers, as a function of disassociation strength of repression.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750523&req=5

Figure 8: Change in mean switching time of toggle switch due to multimerization. Mean switching time of a toggle switch as a function of the inverse repression strength C, where the genetic interactions are implement with different orders of homomers, as a function of disassociation strength of repression.
Mentions: The parameters used in the models were: RNA degradation rate dM = 6 dP, expected transcript number kM N−1dM−1 = 5, transcription kinetics shape αM = 1, expected number of protein per RNA kP dP−1 = 5, and disassociation of repression K = C kM N−1 dM −1 kP dP−1, where C was varied in the range [10−4, 104] with approximately logarithmic spacing (i.e. {a 10b/ a ∈ {1, 2, 3, ⋯ , 9}, b ∈ {−4, −3, −2, ⋯ , 4}}). The gene expression parameters are in agreement with live cell measurements in E. coli [6]. The switch's state was sampled with intervals of 1/30 time units, the simulations provided 106 samples. The mean switching time as a function of the inverse of the repression strength C is shown in Figure 8.

Bottom Line: We show that, although multimerization increases noise by reducing the mean number of functional complexes it can reduce noise in comparison with a monomer, when abundance of the functional proteins are comparable.Alternatively, reduction in noise occurs if both monomeric and multimeric forms of the protein are functional.Moreover, we find that multimerization either increases the response time to external signals or decreases the correlation between number of functional complexes and protein production kinetics.

View Article: PubMed Central - HTML - PubMed

ABSTRACT
We explore whether the process of multimerization can be used as a means to regulate noise in the abundance of functional protein complexes. Additionally, we analyze how this process affects the mean level of these functional units, response time of a gene, and temporal correlation between the numbers of expressed proteins and of the functional multimers. We show that, although multimerization increases noise by reducing the mean number of functional complexes it can reduce noise in comparison with a monomer, when abundance of the functional proteins are comparable. Alternatively, reduction in noise occurs if both monomeric and multimeric forms of the protein are functional. Moreover, we find that multimerization either increases the response time to external signals or decreases the correlation between number of functional complexes and protein production kinetics. Finally, we show that the results are in agreement with recent genome-wide assessments of cell-to-cell variability in protein numbers and of multimerization in essential and non-essential genes in Escherichia coli, and that the effects of multimerization are tangible at the level of genetic circuits.

Show MeSH
Related in: MedlinePlus