CAREER: Selective Recognition and Regulation of Lead(II) by the PbrR Proteins

由无机、生物无机和有机金属化学以及分子和细胞生物学生物化学项目颁发的CAREER奖支持芝加哥大学He Chuan教授对Ralstonia metallidurans CH34中铅（II）离子的选择性识别和调控的研究。这种微生物具有自然界中唯一已知的铅特异性抗性途径。这种独特的途径似乎是由三种PbrR蛋白调节的，它们是由PI的研究小组确定的。这些蛋白是MerR家族金属调节蛋白的成员，它们结合铅（II）离子的选择性比其他金属离子高近1000倍，是已知的最具选择性的铅（II）结合分子之一。PbrRs对铅（II）的特异性识别激活了防御系统，以对抗金属绒螯虾中有毒水平的铅。本研究的目的是揭示PbrR蛋白对铅（II）离子表现出高选择性的潜在机制，并了解金属石斛中铅（II）特异性耐药途径。在研究过程中获得的基础知识将为设计选择性铅（II）螯合剂或探针提供指导。研究将与不同层次的教育相结合；研究生、本科生和高中生将参与跨学科的研究训练。该计划将通过PI和芝加哥大学组织的各种外展活动来介绍。

This CAREER award by the Inorganic, Bioinorganic, and Organometallic Chemistry and Molecular and Cell Biology Biochemistry programs supports work by Professor Chuan He at the University of Chicago to study the selective recognition and regulation of lead(II) ions in Ralstonia metallidurans CH34. This microbe possesses the only known lead-specific resistance pathway in nature. This unique pathway appears to be regulated by three PbrR proteins, which were identified by the PI's research group. These proteins, which are members of the MerR family metalloregulatory proteins, bind lead(II) ion almost 1000-fold more selectively than other metal ions and are among the most selective lead(II)-binding molecules known. The lead(II)-specific recognition by the PbrRs activate the defensive system against toxic levels of lead in R. metallidurans. The objectives of this research are to reveal the underlying mechanism for the high selectivity exhibited by the PbrR proteins towards lead(II) ion and to understand the lead(II)-specific resistance pathway in R. metallidurans. The fundamental knowledge acquired during the course of the research will provide guidance to design selective lead(II) chelators or probes. Research will be integrated with education at different levels; graduate, undergraduate, and high-school students will be involved in the interdisciplinary research training. The program will be presented through various outreach efforts organized by the PI and the University of Chicago.