Allosteric histidine switch for regulation of intracellular zinc(II) fluctuation
Allosteric histidine switch for regulation of intracellular zinc(II) fluctuation
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用于调节细胞内锌 (II) 波动的变构组氨酸开关
DOI：
10.1073/pnas.1708563115
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发表时间：
2017-12
期刊：
影响因子：
--
通讯作者：
Peng R. Chen
中科院分区：
文献类型：
--
作者：
Rongfeng Zhu;Yanqun Song;Haiping Liu;Yufei Yang;Shenlin Wang;Chengqi Yi;Peng R. Chen
意义金属稳态对许多生物过程至关重要，金属调节剂在其调节中起关键作用。在转录调控，这是变构控制的金属调节剂，其金属结合残基和/或相关的氢键网络的重组通常是利用，而在相同的金属结合残基上的配位原子保持很少改变。我们的研究显示了一个例子，锌诱导的转录调节子ZitR开关的组氨酸氮原子之一的锌协调响应锌波动。这种组氨酸开关过程促进ZitR蛋白的构象变化，允许变构和微调控制DNA结合和转录调控。金属调节剂通过金属结合诱导的配体残基和/或氢键网络重组来变构控制转录活性，而相同配体残基上的配位原子仍然很少改变。在这里，我们表明，MarR型锌转录调节子ZitR开关的组氨酸氮原子之一的锌配位过程中的变构控制的DNA结合。ZitR的高亲和力锌位点（位点1）内组氨酸42上的Zn（II）配位氮在Zn（II）结合到其低亲和力锌位点（位点2）时从Nε2转换为Nδ1，这促进了ZitR从非最佳DNA结合构象转换为最佳DNA结合构象。这种组氨酸开关介导的网站1和网站2之间的合作，使ZitR调整其DNA结合亲和力，以响应广泛的锌波动，这可能允许微调的转录调控。
Significance Metal homeostasis is critical to numerous biological processes, and metalloregulators play key roles in its regulation. In transcriptional regulation, which is allosterically controlled by metalloregulators, reorganization of their metal-binding residues and/or related hydrogen bonding networks is usually utilized, while the coordination atoms on the same metal-binding residues remain seldom changed. Our study shows an example whereby the zinc-induced transcriptional regulator ZitR switches one of its histidine nitrogen atoms for zinc coordination in response to zinc fluctuation. This histidine-switch process facilitates conformational change of ZitR protein, allowing allosteric and fine-tuned control of DNA binding and transcriptional regulation. Metalloregulators allosterically control transcriptional activity through metal binding-induced reorganization of ligand residues and/or hydrogen bonding networks, while the coordination atoms on the same ligand residues remain seldom changed. Here we show that the MarR-type zinc transcriptional regulator ZitR switches one of its histidine nitrogen atoms for zinc coordination during the allosteric control of DNA binding. The Zn(II)-coordination nitrogen on histidine 42 within ZitR’s high-affinity zinc site (site 1) switches from Nε2 to Nδ1 upon Zn(II) binding to its low-affinity zinc site (site 2), which facilitates ZitR’s conversion from the nonoptimal to the optimal DNA-binding conformation. This histidine switch-mediated cooperation between site 1 and site 2 enables ZitR to adjust its DNA-binding affinity in response to a broad range of zinc fluctuation, which may allow the fine tuning of transcriptional regulation.
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DOI：
10.1073/pnas.1733691100
发表时间：
2003-08-19
影响因子：
11.1
作者：
Panina, EM;Mironov, AA;Gelfand, MS
通讯作者：
Gelfand, MS
DOI：
10.1073/pnas.1017744108
发表时间：
2011-03-22
影响因子：
11.1
作者：
Shin, Jung-Ho;Jung, Hoi Jong;Roe, Jung-Hye
通讯作者：
Roe, Jung-Hye
影响因子：
16
作者：
Hong, M;Fuangthong, M;Brennan, RG
通讯作者：
Brennan, RG
影响因子：
2.9
作者：
JEFFERSON, JR;HUNT, JB;GINSBURG, A
通讯作者：
GINSBURG, A
影响因子：
5.6
作者：
Reyes-Caballero, Hermes;Guerra, Alfredo J.;Giedroc, David P.
通讯作者：
Giedroc, David P.