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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.

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.

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Cross-correlation between homomers and monomers. Half-life (in units of protein lifetime) of cross-correlation between homomer and monomer levels as a function of the zero-lag (maximum) cross-correlation between the two.
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Figure 7: Cross-correlation between homomers and monomers. Half-life (in units of protein lifetime) of cross-correlation between homomer and monomer levels as a function of the zero-lag (maximum) cross-correlation between the two.

Mentions: To assess these quantities, we sampled the state of the models with intervals of 1/10 of one time unit, and ran the simulations to obtain 105 samples. For each multimer order, we compared the half-life of the protein-homomer cross-correlation with the cross-correlation at zero-lag (Figure 7). The results indicate that for higher orders of multimerization, there is a loss in correlation in the homomers, when the value of the correlation was high. The results indicate that as the order of multimerization increases, the correlation at zero lag of the homomers decreases. This is only significant if these homomers had high cross-correlation to begin with. Moreover, in general, high correlations imply higher half-lives regardless of the order of the multimer, which indicates that the multimers cannot exhibit high control and fast regulation at the same time. Also generally, for multimers with a specific value of correlation at zero lag, lower order multimers will have shorter response times.


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)

Cross-correlation between homomers and monomers. Half-life (in units of protein lifetime) of cross-correlation between homomer and monomer levels as a function of the zero-lag (maximum) cross-correlation between the two.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 7: Cross-correlation between homomers and monomers. Half-life (in units of protein lifetime) of cross-correlation between homomer and monomer levels as a function of the zero-lag (maximum) cross-correlation between the two.
Mentions: To assess these quantities, we sampled the state of the models with intervals of 1/10 of one time unit, and ran the simulations to obtain 105 samples. For each multimer order, we compared the half-life of the protein-homomer cross-correlation with the cross-correlation at zero-lag (Figure 7). The results indicate that for higher orders of multimerization, there is a loss in correlation in the homomers, when the value of the correlation was high. The results indicate that as the order of multimerization increases, the correlation at zero lag of the homomers decreases. This is only significant if these homomers had high cross-correlation to begin with. Moreover, in general, high correlations imply higher half-lives regardless of the order of the multimer, which indicates that the multimers cannot exhibit high control and fast regulation at the same time. Also generally, for multimers with a specific value of correlation at zero lag, lower order multimers will have shorter response times.

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