Adaptation for protein synthesis efficiency in a naturally occurring self-regulating operon.
Adaptation for protein synthesis efficiency in a naturally occurring self-regulating operon.
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DOI：
10.1371/journal.pone.0049678
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Stekel DJ
中科院分区：
文献类型：
--
作者：
Herman D;Thomas CM;Stekel DJ
RK2质粒中的korAB操纵子是一个负协同自我调节操纵子的美丽自然例子。它已经特别好地表征了实验和数学模型。我们已经进行了详细的调查的监管机制的作用，使用生物接地机械多尺度随机模型，其中包括质粒基因调控和复制的背景下，宿主生长和细胞分裂。我们使用该模型来比较四个假设的监管机制的行动：增加鲁棒性的外在因素，减少蛋白质的波动，更快的响应时间的操纵子和减少主机的负担，通过提高效率的蛋白质生产。我们发现，最强的影响的所有元素的监管架构是提高蛋白质合成的效率，减少需要产生的mRNA分子的数量，导致一个大于10倍的减少所需的主机能量来表达这些质粒蛋白。一个较小的，但仍然显着的作用被视为加快响应时间，但这是没有实质性的改善，由协同性。自我调节机制对蛋白质波动和鲁棒性的影响最小。虽然在质粒环境中宿主负荷的减少是明显的，但负自我调节是染色体基因的广泛可见的基序。我们提出，一个重要的进化驱动力的负自我调节基因是提高蛋白质合成的效率。
The korAB operon in RK2 plasmids is a beautiful natural example of a negatively and cooperatively self-regulating operon. It has been particularly well characterized both experimentally and with mathematical models. We have carried out a detailed investigation of the role of the regulatory mechanism using a biologically grounded mechanistic multi-scale stochastic model that includes plasmid gene regulation and replication in the context of host growth and cell division. We use the model to compare four hypotheses for the action of the regulatory mechanism: increased robustness to extrinsic factors, decreased protein fluctuations, faster response-time of the operon and reduced host burden through improved efficiency of protein production. We find that the strongest impact of all elements of the regulatory architecture is on improving the efficiency of protein synthesis by reduction in the number of mRNA molecules needed to be produced, leading to a greater than ten-fold reduction in host energy required to express these plasmid proteins. A smaller but still significant role is seen for speeding response times, but this is not materially improved by the cooperativity. The self-regulating mechanisms have the least impact on protein fluctuations and robustness. While reduction of host burden is evident in a plasmid context, negative self-regulation is a widely seen motif for chromosomal genes. We propose that an important evolutionary driver for negatively self-regulated genes is to improve the efficiency of protein synthesis.
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影响因子：
62.1
作者：
Schreiber, G.;Haran, G.;Zhou, H-X
通讯作者：
Zhou, H-X
影响因子：
64.8
作者：
Becskei, A;Serrano, L
通讯作者：
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影响因子：
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作者：
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通讯作者：
Jenkins DJ
影响因子：
56.9
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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