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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.

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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.

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Change in noise levels due to homodimerization. Relative noise levels of homodimers P1,1 (upper panel) and the total number of molecules  (lower panel) as a function of the noise level of monomers .
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Figure 2: Change in noise levels due to homodimerization. Relative noise levels of homodimers P1,1 (upper panel) and the total number of molecules (lower panel) as a function of the noise level of monomers .

Mentions: Next, using the same models, we compared the noise levels, quantified by the square of the coefficient of variation, denoted by η. The results are shown in Figure 2. When comparing with Figure 1, it is important to note that, in general, models with low and high noise levels correspond to the models with high and low mean levels, respectively. This relationship holds for low mean levels, for which the low-copy number noise dominates, whereas for high mean levels other parameters dominate the noise. The points corresponding to simulations with identical mean levels of X1 are again contiguous, but they do not form vertical lines.


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 noise levels due to homodimerization. Relative noise levels of homodimers P1,1 (upper panel) and the total number of molecules  (lower panel) as a function of the noise level of monomers .
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Change in noise levels due to homodimerization. Relative noise levels of homodimers P1,1 (upper panel) and the total number of molecules (lower panel) as a function of the noise level of monomers .
Mentions: Next, using the same models, we compared the noise levels, quantified by the square of the coefficient of variation, denoted by η. The results are shown in Figure 2. When comparing with Figure 1, it is important to note that, in general, models with low and high noise levels correspond to the models with high and low mean levels, respectively. This relationship holds for low mean levels, for which the low-copy number noise dominates, whereas for high mean levels other parameters dominate the noise. The points corresponding to simulations with identical mean levels of X1 are again contiguous, but they do not form vertical lines.

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