Fang Fang, Lin Yi-Han, Pierce B Daniel, Lynn David G
Departments of Chemistry and Biology, Emory University, Atlanta, GA, 30322, USA.
Chembiochem. 2015 Oct 12;16(15):2183-90. doi: 10.1002/cbic.201500334. Epub 2015 Sep 17.
The molecular logic gates that regulate gene circuits are necessarily intricate and highly regulated, particularly in the critical commitments necessary for pathogenesis. We now report simple AND and OR logic gates to be accessible within a single protein receptor. Pathogenesis by the bacterium Rhizobium radiobacter is mediated by a single histidine kinase, VirA, which processes multiple small molecule host signals (phenol and sugar). Mutagenesis analyses converged on a single signal integration node, and finer functional analyses revealed that a single residue could switch VirA from a functional AND logic gate to an OR gate where each of two signals activate independently. Host range preferences among natural strains of R. radiobacter correlate with these gate logic strategies. Although the precise mechanism for the signal integration node requires further analyses, long-range signal transmission through this histidine kinase can now be exploited for synthetic signaling circuits.
调节基因回路的分子逻辑门必然是复杂且受到高度调控的，尤其是在发病机制所需的关键过程中。我们现在报告，在单个蛋白质受体中可实现简单的“与”门和“或”门逻辑。放射土壤杆菌的致病过程由单个组氨酸激酶VirA介导，它能处理多种小分子宿主信号（苯酚和糖类）。诱变分析集中在一个单一的信号整合节点上，更精细的功能分析表明，单个残基可将VirA从功能性“与”门转变为“或”门，即两个信号中的每一个都能独立激活。放射土壤杆菌自然菌株之间的宿主范围偏好与这些门逻辑策略相关。尽管信号整合节点的确切机制需要进一步分析，但现在可以利用通过这种组氨酸激酶的远程信号传输来构建合成信号回路。
