Carpenter Margaret C, Palmer Amy E
Department of Chemistry and Biochemistry and BioFrontiers Institute, University of Colorado, Boulder, CO 80305, U.S.A.
Essays Biochem. 2017 May 9;61(2):237-243. doi: 10.1042/EBC20160069.
Ca and Zn dynamics have been identified as important drivers of physiological processes. In order for these dynamics to encode function, the cell must have sensors that transduce changes in metal concentration to specific downstream actions. Here we compare and contrast the native metal sensors: calmodulin (CaM), the quintessential Ca sensor and metal-responsive transcription factor 1 (MTF1), a candidate Zn sensor. While CaM recognizes and modulates the activity of hundreds of proteins through allosteric interactions, MTF1 recognizes a single DNA motif that is distributed throughout the genome regulating the transcription of many target genes. We examine how the different inorganic chemistries of these two metal ions may shape these different mechanisms transducing metal ion concentration into changing physiologic activity. In addition to native metal sensors, scientists have engineered sensors to spy on the dynamic changes of metals in cells. The inorganic chemistry of the metals shapes the possibilities in the design strategies of engineered sensors. We examine how different strategies to tune the affinities of engineered sensors mirror the strategies nature developed to sense both Ca and Zn in cells.
钙（Ca）和锌（Zn）动态变化已被确定为生理过程的重要驱动因素。为了使这些动态变化编码功能，细胞必须具有将金属浓度变化转化为特定下游作用的传感器。在这里，我们比较并对比天然金属传感器：钙调蛋白（CaM），典型的钙传感器和金属反应转录因子1（MTF1），一种候选锌传感器。虽然CaM通过变构相互作用识别并调节数百种蛋白质的活性，但MTF1识别分布在整个基因组中的单一DNA基序，调节许多靶基因的转录。我们研究了这两种金属离子的不同无机化学性质如何塑造这些将金属离子浓度转化为生理活性变化的不同机制。除了天然金属传感器外，科学家们还设计了传感器来监测细胞中金属的动态变化。金属的无机化学性质决定了工程传感器设计策略的可能性。我们研究了调整工程传感器亲和力的不同策略如何反映自然界在细胞中感知钙和锌所采用的策略。
