Direct regulation of topoisomerase activity by a nucleoid-associated protein.
Direct regulation of topoisomerase activity by a nucleoid-associated protein.
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DOI：
10.1093/nar/gku804
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发表时间：
2014
影响因子：
14.9
通讯作者：
Nagaraja V
中科院分区：
文献类型：
--
作者：
Ghosh S;Mallick B;Nagaraja V
细菌染色体的拓扑稳态是通过基因组的紧密性和拓扑结构之间的平衡来维持的。两类蛋白质在染色体组织中起主要作用：类核蛋白（NAP）和拓扑异构酶。NAP结合DNA以压缩染色体，而拓扑异构酶催化去除超螺旋或将超螺旋引入基因组。我们证明，HU，结核分枝杆菌的主要NAP特异性地刺激分枝杆菌拓扑异构酶I（TopoI）的DNA松弛能力在较低浓度，但在较高浓度的干扰。M之间的直接物理相互作用。结核杆菌HU（MtHU）和Topo I是增强体外和体内酶活性所必需的。相互作用是在MtHU的氨基末端结构域和TopoI的羧基末端结构域之间。MtHU的结合不影响两个催化酯交换步骤，但增强了DNA链通过，这是完成DNA松弛所必需的，这是一种新的拓扑异构酶活性调节机制。MtHU的相互作用缺陷突变体在增强链通过活性方面受到损害。MtHU和TopoI之间的物种特异性物理和功能合作可能是实现维持分枝杆菌基因组最佳超螺旋密度所需的DNA松弛水平的关键。
The topological homeostasis of bacterial chromosomes is maintained by the balance between compaction and the topological organization of genomes. Two classes of proteins play major roles in chromosome organization: the nucleoid-associated proteins (NAPs) and topoisomerases. The NAPs bind DNA to compact the chromosome, whereas topoisomerases catalytically remove or introduce supercoils into the genome. We demonstrate that HU, a major NAP of Mycobacterium tuberculosis specifically stimulates the DNA relaxation ability of mycobacterial topoisomerase I (TopoI) at lower concentrations but interferes at higher concentrations. A direct physical interaction between M. tuberculosis HU (MtHU) and TopoI is necessary for enhancing enzyme activity both in vitro and in vivo. The interaction is between the amino terminal domain of MtHU and the carboxyl terminal domain of TopoI. Binding of MtHU did not affect the two catalytic trans-esterification steps but enhanced the DNA strand passage, requisite for the completion of DNA relaxation, a new mechanism for the regulation of topoisomerase activity. An interaction-deficient mutant of MtHU was compromised in enhancing the strand passage activity. The species-specific physical and functional cooperation between MtHU and TopoI may be the key to achieve the DNA relaxation levels needed to maintain the optimal superhelical density of mycobacterial genomes.
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影响因子：
3.9
作者：
Godbole, Adwait Anand;Leelaram, Majety Naga;Nagaraja, Valakunja
通讯作者：
Nagaraja, Valakunja
影响因子：
4.8
作者：
Espeli, O;Lee, C;Marians, KJ
通讯作者：
Marians, KJ
DOI：
10.1073/pnas.0611686104
发表时间：
2007-03-13
影响因子：
11.1
作者：
Guo, Fusheng;Adhya, Sankar
通讯作者：
Adhya, Sankar
影响因子：
16.6
作者：
Bhowmick, Tuhin;Ghosh, Soumitra;Nagaraja, Valakunja
通讯作者：
Nagaraja, Valakunja
影响因子：
11.4
作者：
Aki, T;Adhya, S
通讯作者：
Adhya, S