Giedroc David P, Arunkumar Alphonse I
Department of Biochemistry and Biophysics, Texas A&M University, 2128 TAMU, College Station, TX 77843-2128, USA.
Dalton Trans. 2007 Aug 7(29):3107-20. doi: 10.1039/b706769k. Epub 2007 Jun 28.
Metalloregulatory proteins control the expression of genes that allow organisms to quickly adapt to chronic toxicity or deprivation of both biologically essential metal ions and heavy metal pollutants found in their microenvironment. Emerging evidence suggests that metal ion homeostasis and resistance defines an important tug-of-war in human host-bacterial pathogen interactions. This adaptive response originates with the formation of "metal receptor" complexes of exquisite selectivity. In this perspective, we summarize consensus structural features of metal sensing coordination complexes and the evolution of distinct metal selectivities within seven characterized metal sensor protein families. In addition, we place recent efforts to understand the structural basis of metal-induced allosteric switching of these metalloregulatory proteins in a thermodynamic framework, and review the degree to which coordination chemistry drives changes in protein structure and dynamics in selected metal sensor systems. New insights into how metal sensor proteins function in the complex intracellular milieu of the cytoplasm of cells will require a more sophisticated understanding of the "metallome" and will benefit greatly from ongoing collaborative efforts in bioinorganic, biophysical and analytical chemistry, structural biology and microbiology.
金属调节蛋白控制着一些基因的表达，这些基因使生物体能够快速适应其微环境中生物必需金属离子和重金属污染物的慢性毒性或缺乏。新出现的证据表明，金属离子稳态和抗性在人类宿主与细菌病原体的相互作用中定义了一场重要的较量。这种适应性反应源于具有高度选择性的“金属受体”复合物的形成。从这个角度出发，我们总结了金属传感配位复合物的共识结构特征以及七个已表征的金属传感器蛋白家族中不同金属选择性的演变。此外，我们将最近为理解这些金属调节蛋白的金属诱导变构转换的结构基础所做的努力置于一个热力学框架中，并回顾了配位化学在选定的金属传感器系统中驱动蛋白质结构和动力学变化的程度。要深入了解金属传感器蛋白在细胞复杂的细胞质内环境中的功能，需要对“金属组”有更深入的理解，并且将极大地受益于生物无机化学、生物物理与分析化学、结构生物学和微生物学领域正在进行的合作努力。
