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Cyclic AMP binding to a universal stress protein in Mycobacterium tuberculosis is essential for viability
Journal of Biological Chemistry ( IF 5.5 ) Pub Date : 2024-04-16 , DOI: 10.1016/j.jbc.2024.107287
Arka Banerjee , Moubani Chakraborty , Suruchi Sharma , Ruchi Chaturvedi , Avipsa Bose , Priyanka Biswas , Amit Singh , Sandhya S. Visweswariah

Mycobacterial genomes encode multiple adenylyl cyclases and cAMP effector proteins, underscoring the diverse ways these bacteria utilize cAMP. We identified universal stress proteins, Rv1636 and MSMEG_3811 in and respectively, as abundantly expressed, novel cAMP-binding proteins. Rv1636 is secreted the SecA2 secretion system in but is not directly responsible for the efflux of cAMP from the cell. In slow-growing mycobacteria, intrabacterial concentrations of Rv1636 were equivalent to the concentrations of cAMP present in the cell. In contrast, levels of intrabacterial MSMEG_3811 in were lower than that of cAMP and therefore, overexpression of Rv1636 increased levels of “bound” cAMP. While could be readily deleted from the genome of , we found that the gene is essential for the viability of and is dependent on the cAMP-binding ability of Rv1636. Therefore, Rv1636 may function to regulate cAMP signaling by direct sequestration of the second messenger. This is the first evidence of a “sponge” for any second messenger in bacterial signaling that would allow mycobacterial cells to regulate the available intrabacterial “free” pool of cAMP.

中文翻译:


环 AMP 与结核分枝杆菌中的通用应激蛋白结合对于生存至关重要



分枝杆菌基因组编码多种腺苷酸环化酶和 cAMP 效应蛋白,强调了这些细菌利用 cAMP 的多种方式。我们分别鉴定了通用应激蛋白 Rv1636 和 MSMEG_3811,它们是丰富表达的新型 cAMP 结合蛋白。 Rv1636 由 SecA2 分泌系统分泌,但并不直接负责 cAMP 从细胞中的流出。在生长缓慢的分枝杆菌中,Rv1636 的细菌内浓度相当于细胞中存在的 cAMP 浓度。相反,细菌内 MSMEG_3811 的水平低于 cAMP,因此,Rv1636 的过度表达增加了“结合”cAMP 的水平。虽然可以很容易地从 Rv1636 的基因组中删除,但我们发现该基因对于 Rv1636 的生存至关重要,并且依赖于 Rv1636 的 cAMP 结合能力。因此,Rv1636 可能通过直接隔离第二信使来调节 cAMP 信号传导。这是细菌信号传导中任何第二信使的“海绵”的第一个证据,它允许分枝杆菌细胞调节细菌内可用的“游离”cAMP池。
更新日期:2024-04-16
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