METALLOREGULATION BY MERR AND FUR PROTEIN FAMILIES

Merr 和毛皮蛋白家族的金属调节

• 批准号: 6860999
• 负责人: THOMAS V O'HALLORAN
• 金额: $ 29.77万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-07-01 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6860999
• 关键词: Escherichia coli; bacterial proteins; binding proteins; chemical kinetics; copper; iron; metal metabolism; microorganism culture; microorganism metabolism; protein structure function; thermodynamics; transcription factor; zinc

DESCRIPTION (applicant's description): Metal ion sensory mechanisms are critical for cellular responses 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 antibiotic treatments. 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 beginning to provide insights into 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 interactions induce distortions in DNA structure that make the DNA a better template for 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 insights of these new stress-responsive transcription factors will provide a deeper understanding of molecular mechanisms and transition metal cell biology.

描述（申请人描述）：金属离子的感觉机制是