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Stability in numbers

By blocking degradation, dimerization may extend the range at which a bistable circuit operates. BUCHLER

Two subunits are better than one when the goal is a bistable or oscillating circuit. The findings, based on a mathematical model by Nicolas Buchler (The Rockefeller University, New York, NY) and colleagues, suggest another reason why homodimers are common in biology. "When dimers are more stable than monomers," says Buchler, "it can have a big impact on genetic circuits."

Experimental evidence has shown that dimerization can hide a proteolytic tag or stabilize unfolded monomers. For such proteins, the degradation rate will decrease as the concentration of the protein (and thus of its dimer) increases. Buchler et al. modeled the effect of this cooperative stability in a simple, bistable bacterial genetic circuit in which a transcription factor dimer activates its own gene expression.

This bistable circuit can settle in either of two states at a high or low protein level, respectively. For typical transcription factors at physiological conditions, the bacterial cell was shown to have only two to ten dimers per cell. "For the high state, that's not many molecules," says Buchler. "The circuit will be susceptible to stochastic noise."

Cooperative stability relieved this problem. By elevating the degradation rate of the monomers ten-fold, the same circuit could now be bistable at higher concentrations. The high state increased to 100 molecules, thus reducing the susceptibility of the bistable circuit to stochastic fluctuations.

Since many other proteins (e.g., enzymes, kinases) can form dimers, cooperative stability might also influence metabolic or signaling networks. "We still need experiments to know how common this is," says Buchler. "But we hope our results highlight the potential consequences of dimerization and degradation of regulatory proteins".

Reference:

Buchler, N., et al. 2005. Proc. Natl. Acad. Sci. USA. doi:10.1073/pnas.0409553102.[Abstract/Free Full Text]

Nicole LeBrasseur

lebrasn{at}rockefeller.edu

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This Article PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by LeBrasseur, N. Search for Related Content PubMed Articles by LeBrasseur, N. Social Bookmarking                            What's this?