Metalloregulation by MerR and Fur Protein Families

金属离子的感觉机制对于细胞对必需金属和有毒金属的反应都是至关重要的。新兴 从微生物金属调控系统的研究中得出的一般模型可以作为以下研究的起点 了解人类体内金属的细胞生物学。金属调节蛋白的Merr和Fur家族 控制一系列保护真细菌细胞免受物理和化学压力的基因的表达 包括抗生素治疗。在各种有毒微生物中，毛皮或与之密切相关的铁感受器蛋白 控制毒素的表达。铁反应去阻遏的一种普遍但有争议的机制是 已提出，但截至目前尚未解决。 对这些汞和铁感受器蛋白的机制研究现在开始提供对锌的洞察 以及对铜反应的金属调节。新近发现的MERR成员--E.ColiZntR蛋白 家族，是一种锌特异的金属调节蛋白，控制锌出口机制的表达。它的 与之对应的是Zur蛋白，它是Fur家族的成员，对表达施加锌反应控制 锌摄取机器。这些基因共同控制锌的吸收和输出，确保细胞经历 既不缺锌，也不中毒。在这两种情况下，转录控制的机制或分子基础 对金属的识别还没有建立起来。 这项建议侧重于金属识别和金属诱导的能量和结构方面 变构转换机制中的构象变化。Merr以前所未有的方式控制转录 方式：金属-蛋白质相互作用导致DNA结构扭曲，使DNA成为更好的模板 转录机器。通过比较其他家族成员的正向控制机制，如ZntR，a 对这种DNA扭曲机制的全面测试是可能的。积极的控制机制很差 对于理解基因调控的分子基础，了解并仍然具有根本性的重要性。 重金属识别的分子基础将在以下几个方面进行探讨 生物聚合物和配位化学水平。这些新压力的结构、功能和能量洞察力- 有反应的转录因子将提供对分子机制和过渡金属的更深层次的理解 细胞生物学。

Metal ion sensory mechanisms are critical for cellularresponses to essential and toxic metals alike. Emerging from studies of microbial metalloregulatory systems are general models that serve as starting points for understanding the cell biology of metals in humans. The MerR and Fur families of metalloregulatory proteins control the expression of an array of genes that protect the eubacterial cell from physical and chemical stresses including antibiotictreatments. In a variety of virulent microbes, Fur or a closely related iron-sensor protein controls toxin expression. A general but controversial mechanism for iron-responsive derepression has been proposed but is as of yet unresolved. Mechanistic studies of these mercury and iron sensor proteins are now beginningto provide insightsinto zinc and copper-responsive metalloregulation. The E. coli ZntR protein, a recently discovered member of the MerR family, is a zinc-specific metalloregulatory protein that controls expression of zinc export machinery. Its counterpart, the Zur protein, is a member of the Fur family that exerts zinc-responsive control over the expression of zinc uptake machinery. Together these genes govern zinc uptake and export, ensuring that cells experience neither zinc starvation nor toxicity. In both cases the mechanisms of transcriptional control or the molecular basis of metal recognition are not yet established. This proposal focuses on energetic and structural aspects of metal recognition and metal-induced conformation changes in the allosteric switching mechanism. MerR controls transcription in an unprecedented manner: metal-protein interactionsinduce distortions in DNA structure that make the DNA a better templatefor the transcription machinery. By comparing the positive control mechanism for other family members such as ZntR, a comprehensive test of this DNA distortion mechanism is possible. Positive control mechanisms are poorly understood and yet are of fundamental importance in understanding the molecular basis of genetic regulation. The molecular basis of heavy metal recognition in the ZntR, Zur, and Fur systems will be probed at the biopolymer and coordination chemistry levels. The structure, function, and energetic insightsof these new stress- responsive transcription factors will provide a deeper understanding of molecular mechanisms and transition metal cell biology.