A systems approach to model natural variation in reactive properties of bacterial ribosomes

利用系统方法模拟细菌核糖体反应特性的自然变异

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Abstract

BACKGROUND: Natural variation in protein output from translation in bacteria and archaea may be an organism-specific property of the ribosome. This paper adopts a systems approach to model the protein output as a measure of specific ribosome reactive properties in a ribosome-mediated translation apparatus. We use the steady-state assumption to define a transition state complex for the ribosome, coupled with mRNA, tRNA, amino acids and reaction factors, as a subsystem that allows a focus on the completed translational output as a measure of specific properties of the ribosome. RESULTS: In analogy to the steady-state reaction of an enzyme complex, we propose a steady-state translation complex for mRNA from any gene, and derive a maximum specific translation activity, Ta(max), as a property of the ribosomal reaction complex. Ta(max) has units of a-protein output per time per a-specific mRNA. A related property of the ribosome, T a(max), has units of a-protein per time per total RNA with the relationshipT a(max) = rho(a)Ta(max), where rho(a) represents the fraction of total RNA committed to translation outpout of P(a) from gene a message. Ta(max) as a ribosome property is analogous to k(cat) for a purified enzyme, and Ta(max) is analogous to enzyme specific activity in a crude extract. CONCLUSION: Analogy to an enzyme reaction complex led us to a ribosome reaction model for measuring specific translation activity of a bacterial ribosome. We propose to use this model to design experimental tests of our hypothesis that specific translation activity is a ribosomal property that is subject to natural variation and natural selection much like Vmax and Km for any specific enzyme.

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