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 noise levels of homomers due to higher-order multimerization. Relative noise levels of homomers (with adjusted kM to compensate for the reduction in the mean level) with multimerization of different orders as a function of the noise level of monomers . The dashed lines indicate gains of unity, one half, one third, one quarter, and one fifth.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: Change in noise levels of homomers due to higher-order multimerization. Relative noise levels of homomers (with adjusted kM to compensate for the reduction in the mean level) with multimerization of different orders as a function of the noise level of monomers . The dashed lines indicate gains of unity, one half, one third, one quarter, and one fifth.

Mentions: We also compared noise levels of strictly monomeric proteins to those of multimers. For this comparison, the transcription rate of the proteins composing the multimers are chosen so that the mean numbers of the multimer form are similar to those of the strict monomer. The results (Figure 6) are similar to the homodimer case (Figure 4). Potentially, this scheme allows the noise level to be suppressed to N−1th of the original value, but this is only achievable for highly expressed genes. In general, higher-order multimerization can only lead to noise suppression within a limited range of parameter values. More specifically, in the case of high order multimers, the fluctuations in protein numbers alone determines if the noise in multimer numbers is amplified or suppressed.


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 of homomers due to higher-order multimerization. Relative noise levels of homomers (with adjusted kM to compensate for the reduction in the mean level) with multimerization of different orders as a function of the noise level of monomers . The dashed lines indicate gains of unity, one half, one third, one quarter, and one fifth.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: Change in noise levels of homomers due to higher-order multimerization. Relative noise levels of homomers (with adjusted kM to compensate for the reduction in the mean level) with multimerization of different orders as a function of the noise level of monomers . The dashed lines indicate gains of unity, one half, one third, one quarter, and one fifth.
Mentions: We also compared noise levels of strictly monomeric proteins to those of multimers. For this comparison, the transcription rate of the proteins composing the multimers are chosen so that the mean numbers of the multimer form are similar to those of the strict monomer. The results (Figure 6) are similar to the homodimer case (Figure 4). Potentially, this scheme allows the noise level to be suppressed to N−1th of the original value, but this is only achievable for highly expressed genes. In general, higher-order multimerization can only lead to noise suppression within a limited range of parameter values. More specifically, in the case of high order multimers, the fluctuations in protein numbers alone determines if the noise in multimer numbers is amplified or suppressed.

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