Allosteric histidine switch for regulation of intracellular zinc(II) fluctuation

作者：Zhu, Rongfeng; Song, Yanqun; Liu, Haiping; Yang, Yufei; Wang, Shenlin; Yi, Chengqi; Chen, Peng R.^*

来源：Proceedings of the National Academy of Sciences of the United States of America, 2017, 114(52): 13661-13666.

DOI：10.1073/pnas.1708563115

• histidine switch
• zinc homeostasis
• allostery
• transcription factors
• X-ray crystallography

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 N epsilon 2 to N delta 1 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.

• 出版日期2017-12-26
• 单位中国科学院; 北京大学; 中国科学院天津工业生物技术研究所