Cyanobacteria are responsible for up to 80% of aquatic carbon dioxide fixation and have evolved specialized carbon concentrating mechanism to increase photosynthetic yield. As such, cyanobacteria are attractive targets for synthetic biology and engineering approaches to address the demands of global energy security, food production, and climate change for an increasing world's population. The bicarbonate transporter BicA is a sodium-dependent, low-affinity, high-flux bicarbonate symporter expressed in the plasma membrane of cyanobacteria. Despite extensive biochemical characterization of BicA, including the resolution of the BicA crystal structure, the dynamic understanding of the bicarbonate transport mechanism remains elusive. To this end, we have collected over 1 ms of all-atom molecular dynamics simulation data of the BicA dimer to elucidate the structural rearrangements involved in the substrate transport process. We further characterized the energetics of the transition of BicA protomers and investigated potential mutations that are shown to decrease the free energy barrier of conformational transitions. In all, our study illuminates a detailed mechanistic understanding of the conformational dynamics of bicarbonate transporters and provide atomistic insights to engineering these transporters for enhanced photosynthetic production.

中文翻译：

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蓝细菌碳酸氢盐转运蛋白 BicA 的 Elevator 型机制的分子见解。


蓝细菌负责高达 80% 的水生二氧化碳固定，并已进化出专门的碳浓缩机制来提高光合作用产量。因此，蓝藻是合成生物学和工程方法的有吸引力的目标，以满足全球能源安全、粮食生产和气候变化对世界不断增长的人口的需求。碳酸氢盐转运蛋白 BicA 是一种钠依赖性、低亲和力、高通量的碳酸氢盐同向转运蛋白，在蓝细菌的质膜中表达。尽管 BicA 具有广泛的生化表征，包括 BicA 晶体结构的分辨率，但对碳酸氢盐转运机制的动力学理解仍然难以捉摸。为此，我们收集了超过 1 ms 的 BicA 二聚体全原子分子动力学模拟数据，以阐明底物传输过程中涉及的结构重排。我们进一步表征了 BicA 原聚体转变的能量学，并研究了被证明会降低构象转变的自由能屏障的潜在突变。总而言之，我们的研究阐明了对碳酸氢盐转运蛋白构象动力学的详细机制理解，并为设计这些转运蛋白以增强光合作用产生提供了原子学见解。