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化学进展 2019, Vol. 31 Issue (10): 1372-1383 DOI: 10.7536/PC190310 前一篇   后一篇

• •

金属调控蛋白的结构、性质及应用

郑亚楠, 王丹**()   

  1. 南宁师范大学化学与材料学院 南宁 530001
  • 收稿日期:2019-03-12 出版日期:2019-10-15 发布日期:2019-08-05
  • 通讯作者: 王丹
  • 基金资助:
    国家自然科学基金青年基金项目(31800631); 广西自然科学基金青年基金项目(2018JJB120049); 广西高校中青年教师基础能力提升项目(2018KY0361)
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Structures, Properties, and Applications of Metalloregulatory Proteins

Yanan Zheng, Dan Wang**()   

  1. College of Chemistry and Materials, Nanning Normal University, Nanning 530001, China
  • Received:2019-03-12 Online:2019-10-15 Published:2019-08-05
  • Contact: Dan Wang
  • About author:
    ** E-mail:
  • Supported by:
    National Natural Science Foundation of China(31800631); Natural Science Foundation of Guangxi Province(2018JJB120049); Middle-aged and Young Teachers’ Basic Ability Promotion Project of Guangxi(2018KY0361)

金属调控蛋白是微生物体内通过转录抑制或激活机制严格控制金属离子摄入、外排和储存的特异性金属离子结合蛋白,对维持体内适宜的金属离子浓度和平衡起着举足轻重的作用。本文综述了目前主要的七大家族金属调控蛋白的调控机制和拓扑结构,详细介绍了金属离子结合区域的结构特征和金属-配体的配位构型。基于金属-配体的配位构型,重点讨论了每类金属调控蛋白对目标金属离子特异性选择的机理。此外,本文还介绍了金属调控蛋白在重金属离子检测和吸附方面的应用,拓展了金属调控蛋白的研究和应用领域,同时为生物无机化学的研究方向开辟了新的思路。

关键词： 金属调控蛋白, 金属离子, 调控机制, 拓扑结构, 配位构型

The metalloregulatory protein is the metal-specific binding protein in microorganisms that tightly regulates the intake, efflux, and storage of the metal ions through the regulatory mechanism of transcriptional repression or activation, which is particularly important for the maintaining of suitable metal concentration and homeostasis. In this review, the regulatory mechanism and topological structure are summarized within the current seven major families of metalloregulatory proteins, and the structural feature and metal-ligand coordination geometry of metal-binding domain are also introduced in detail. Based on the metal-ligand coordination geometry, the mechanisms are discussed for the metal selectivity of metalloregulatory proteins. In addition, the applications of metalloregulatory proteins in metal-ion detection and adsorption are also introduced, which not only broadens the research and application areas of metalloregulatory proteins, but also exploits new direction for the bioinorganic chemistry research.

Key words: metalloregulatory protein, metal ions, regulatory mechanism, topological structure, coordination geometry
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图1 枯草芽孢杆菌PerR蛋白的晶体结构示意图,上图为金属调控蛋白PerR的氧化状态,命名为PerR-Zn-ox(PDB: 2RGV),下图为金属调控蛋白PerR的激活状态,命名为PerR-Zn-Mn(PDB: 3F8N)
Fig. 1 Ribbon diagrams of crystallographic structures of B. subtilis PerR. The oxidized form of PerR, designated PerR-Zn-ox, is shown in the top. The Mn(Ⅱ)-activated PerR, designated PerR-Zn-Mn, is shown in the bottom
图2 枯草杆菌MntR蛋白的晶体结构示意图及金属离子结合位点:脱辅基的MntR蛋白(PDB: 2HYF)N端DNA结合区域用绿色表示,与金属离子结合的MntR蛋白(PDB: 2F5F) N端的DNA结合区域用蓝色表示
Fig. 2 Ribbon diagrams of crystallographic structures and metal-binding sites of B. subtilis MntR. The N-terminal DNA-binding domain of apo-MntR(PDB: 2HYF) is shown as green, and the N-terminal DNA-binding domain of metal-bound MntR(PDB: 2F5F) is shown as blue
图3 大肠杆菌DNA-Ni(Ⅱ)-NikR三元复合物的蛋白质晶体结构示意图
Fig. 3 Ribbon diagrams of crystallographic structures of E. coli DNA-Ni(Ⅱ)-NikR complex
图4 大肠杆菌CueR蛋白的晶体结构示意图:左图为CueR蛋白未结合目标金属离子的结构示意图,右图为CueR蛋白结合目标金属离子的结构示意图
Fig. 4 Ribbon diagrams of crystallographic structures of E. coli CueR. The metal-free CueR is shown on the left, and the metal-bound CueR is shown on the right
图5 基于S. aureus pI258 CadC蛋白结构绘制的ArsR/SmtB家族金属调控蛋白的金属离子结合位点: S. aureus pI258 CadC蛋白中Zn2+结合位点α5及Cd2+结合位点α3 N在右列图中标注,分别对应左列图中红色和黄色标注的部分;其他ArsR/SmtB家族的金属调控蛋白中金属离子对应的结合位点在左列图中标注
Fig. 5 Summary of the known metal binding sites of ArsR/SmtB family repressors on the structure of S. aureus pI258 CadC homodimer. The Zn(Ⅱ)-binding site α5 and Cd(Ⅱ)-binding site in pI258 CadC homodimer α3 N are shown in the right, which correspond to the red and yellow part in the left. Other metal-binding sites in the ArsR/SmtB family repressors are shown in the left
图6 基于结核分支杆菌CosR蛋白绘制的CosR/RcnR 家族金属调控蛋白的金属离子结合位点和特征序列区域: 结核分支杆菌CosR蛋白与Cu+通过氨基酸残基Cys36、His61’及Cys65’配位,大肠杆菌RcnR蛋白与Ni2+通过特征序列W-X-Y-Z氨基酸残基配位
Fig. 6 Summary of the known metal binding sites and feature sequence domain of CosR/RcnR family repressors on the structure of M. tuberculosis CosR. The M. tuberculosis CosR coordinate Cu(Ⅰ) through the residues Cys36, His61’ and Cys65’. The E. coli RcnR coordinate Ni(Ⅱ) through the residues in the feature sequence domain W-X-Y-Z
图7 (a)基于MerR家族的金属调控蛋白MerR/CueR/PbrR转录调控时“DNA扭曲机制”设计的荧光探针;(b)对金属调控蛋白NikR的蛋白质工程改造[77~79, 83]
Fig. 7 (a) The designed fluorescence probe based on the allosteric transcriptional regulation mechanism of MerR family members MerR, CueR, and PbrR.(b) The protein engineering based on the metalloregulatory protein NikR [77~79, 83]
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