An oligopeptide transporter of Mycobacterium tuberculosis regulates cytokine release and apoptosis of infected macrophages.
An oligopeptide transporter of Mycobacterium tuberculosis regulates cytokine release and apoptosis of infected macrophages.
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DOI：
10.1371/journal.pone.0012225
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发表时间：
2010-08-17
期刊：
影响因子：
3.7
通讯作者：
Basu J
中科院分区：
文献类型：
--
作者：
Dasgupta A;Sureka K;Mitra D;Saha B;Sanyal S;Das AK;Chakrabarti P;Jackson M;Gicquel B;Kundu M;Basu J
结核分枝杆菌基因组编码由Rv 3665 c-Rv 3662 c和Rv 1280 c-Rv 1283 c编码的两种肽转运蛋白。两者都属于ABC转运蛋白家族，含有两个核苷酸结合亚基、两个整合膜蛋白和一个底物结合多肽。然而，对它们在M中的作用知之甚少。结核在这里，我们报告的Rv 1280 c-Rv 1283 c编码的转运蛋白及其底物结合多肽OppAMTB的功能表征。OppAMTB能够结合三肽谷胱甘肽和九肽缓激肽，表明底物特异性较宽。位于OppA结构域I和III之间的界面的氨基酸残基G109、N110、N230、D494和F496是最佳肽结合所需的。互补的一个oppA敲除突变的M。Smeglavin与OppAMTB的比较证实了该转运蛋白在输入谷胱甘肽中的作用以及上述氨基酸残基在肽转运中的重要性。有趣的是，这种转运蛋白调节M。与未感染的巨噬细胞相比，结核病感染者的谷胱甘肽水平较低。这种能力被oppD的失活部分抵消。同时，oppD的失活与感染的巨噬细胞中甲基乙二醛的水平降低和突变体的凋亡诱导能力降低有关。oppD失活后，诱导细胞因子IL-1β、IL-6和TNF-α产生的能力也受到损害。总之，这些研究揭示了新的观察结果，这种肽转运蛋白调节感染M.结核
The Mycobacterium tuberculosis genome encodes two peptide transporters encoded by Rv3665c-Rv3662c and Rv1280c-Rv1283c. Both belong to the family of ABC transporters containing two nucleotide-binding subunits, two integral membrane proteins and one substrate-binding polypeptide. However, little is known about their functions in M. tuberculosis. Here we report functional characterization of the Rv1280c-Rv1283c-encoded transporter and its substrate-binding polypeptide OppAMTB. OppAMTB was capable of binding the tripeptide glutathione and the nonapeptide bradykinin, indicative of a somewhat broad substrate specificity. Amino acid residues G109, N110, N230, D494 and F496, situated at the interface between domains I and III of OppA, were required for optimal peptide binding. Complementaton of an oppA knockout mutant of M. smegmatis with OppAMTB confirmed the role of this transporter in importing glutathione and the importance of the aforesaid amino acid residues in peptide transport. Interestingly, this transporter regulated the ability of M. tuberculosis to lower glutathione levels in infected compared to uninfected macrophages. This ability was partly offset by inactivation of oppD. Concomitantly, inactivation of oppD was associated with lowered levels of methyl glyoxal in infected macrophages and reduced apoptosis-inducing ability of the mutant. The ability to induce the production of the cytokines IL-1β, IL-6 and TNF-α was also compromised after inactivation of oppD. Taken together, these studies uncover the novel observations that this peptide transporter modulates the innate immune response of macrophages infected with M. tuberculosis.
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影响因子：
3.7
作者：
Rachman H;Kim N;Ulrichs T;Baumann S;Pradl L;Nasser Eddine A;Bild M;Rother M;Kuban RJ;Lee JS;Hurwitz R;Brinkmann V;Kosmiadi GA;Kaufmann SH
通讯作者：
Kaufmann SH
影响因子：
4.1
作者：
THORNALLEY, PJ
通讯作者：
THORNALLEY, PJ
影响因子：
16
作者：
Kim, You-Sun;Morgan, Michael J.;Liu, Zheng-Gang
通讯作者：
Liu, Zheng-Gang
影响因子：
4.8
作者：
Alberto Flores-Valdez, Mario;Morris, Rowan P.;Schoolnik, Gary K.
通讯作者：
Schoolnik, Gary K.
影响因子：
11.4
作者：
Berntsson, Ronnie P-A;Doeven, Mark K.;Slotboom, Dirk-Jan
通讯作者：
Slotboom, Dirk-Jan