Characterization of an interplay between a Mycobacterium tuberculosis MazF homolog, Rv1495 and its sole DNA topoisomerase I.
Characterization of an interplay between a Mycobacterium tuberculosis MazF homolog, Rv1495 and its sole DNA topoisomerase I.
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DOI：
10.1093/nar/gkq737
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发表时间：
2010-12
影响因子：
14.9
通讯作者：
He ZG
中科院分区：
文献类型：
--
作者：
Huang F;He ZG
MazEF 系统被认为有助于在人类病原体结核分枝杆菌中观察到的长期休眠能力。然而，除了它们作为 mRNA 干扰酶的功能外，人们对这些系统在病原体中的任何其他细胞功能知之甚少。在本研究中，我们观察到 MazF 蛋白 Rv1495 和唯一的结核分枝杆菌 DNA 拓扑异构酶 I (MtbTopA) 在蛋白质功能方面存在负相互作用。 MtbTopA 通过其 C 端结构域与 Rv1495 发生物理相互作用并抑制 Rv1495 的 mRNA 切割活性。 Rv1495 反过来又抑制 MtbTopA 的 DNA 切割活性及其松弛超螺旋 DNA 的功能。 Rv1495 的 N 末端片段（命名为 Rv1495-N(29-56)）失去了 mRNA 切割活性，但保留了对结核分枝杆菌和耻垢分枝杆菌的 TopA 蛋白的显着物理相互作用和抑制作用。该片段虽然不如全长蛋白有效，但当通过耻垢分枝杆菌中的重组质粒表达时，能够抑制分枝杆菌生长。 Rv1495 在体外和体内均与耻垢分枝杆菌 TopA 发生物理相互作用。我们的研究结果表明，MazEF 系统可以通过一种允许直接调节结核分枝杆菌拓扑异构酶 I 的新机制来影响细菌的存活。
The MazEF systems are thought to contribute to the capacity for long-term dormancy observed in the human pathogen, Mycobacterium tuberculosis. However, except for their functions as mRNA interferases, little is known regarding any additional cellular functions of these systems in the pathogen. In the present study, we observed a negative interplay between MazF protein Rv1495 and the sole M. tuberculosis DNA topoisomerase I (MtbTopA) with respect to protein functions. Through its C-terminal domain, MtbTopA physically interacted with and inhibited the mRNA cleavage activity of Rv1495. Rv1495, in turn, inhibited the DNA cleavage activity of MtbTopA as well as its function of relaxation of supercoiled DNA. An N-terminus fragment of Rv1495, designated Rv1495-N(29-56), lost mRNA cleavage activity, but retained a significant physical interaction and inhibitory effect on TopA proteins from both M. tuberculosis and M. smegmatis. This fragment, although less effective than the full-length protein, was able to inhibit mycobacterial growth when expressed through a recombinant plasmid in M. smegmatis. The Rv1495 physically interacted with the M. smegmatis TopA both in vitro and in vivo. Our findings imply that MazEF systems can affect bacterial survival by a novel mechanism that allows direct modulation of M. tuberculosis topoisomerase I.
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影响因子：
3.2
作者：
Baaklini, Imad;Usongo, Valentine;Drolet, Marc
通讯作者：
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影响因子：
14.9
作者：
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DOI：
10.1073/pnas.83.23.8952
发表时间：
1986-12-01
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
6.7
作者：
Colangeli, Roberto;Helb, Danica;Vilcheze, Catherine;Hazbon, Manzour Hernando;Lee, Chee-Gun;Safi, Hassan;Sayers, Brendan;Sardone, Irene;Jones, Marcus B;Fleischmann, Robert D;Peterson, Scott N;Jacobs, William R Jr;Alland, David
通讯作者：
Alland, David