STUDIES OF MOLECULAR STRUCTURES OF HEME BINDING PROTEINS FROM PATHOGENIC BACTERI

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 血红素是寄主体内病原体必需铁的最大来源。然而，铁被宿主隔离，以防止它被入侵的细菌滥用。因此，病原体进化出了高亲和力的摄取系统，可以特异性地识别和摄取宿主的血红素。金黄色葡萄球菌的ISD(铁表面决定蛋白)家族和空肠弯曲菌的CHA(空肠弯曲菌血红素获取)蛋白是典型的血红素转运系统的组成部分。了解这些转运系统的分子机制的结构基础仍然缺乏。最近在SSRL收集的关于Chan的数据已经被用来确定血红素结合蛋白的结构，这证明了一种新的依赖于血红素的二聚化模型。将测定Chan突变体的晶体结构，以探索特定残基在依赖于血红素的二聚化以及与其他CHA运输成分相互作用中的作用。ISD蛋白的一个血红素结合域的初步晶体已经生产出来，并将被优化用于高分辨结构测定。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Heme is the greatest source of essential iron for pathogens residing within a host. However, the iron is sequestered by the host to prevent its misuse by invading bacteria. Therefore, pathogens have evolved high affinity uptake systems that can specifically recognize and take up host heme. The Isd (iron surface determinant) family of proteins from Staphylococcus aureus and the Cha (Campylobacter heme acquisition) proteins from Campylobacter jejuni are components of characterized heme transport systems. The structural basis for understanding the molecular mechanism of these transport systems is still lacking. Data collected recently on ChaN at the SSRL has been used to determine the structure of the heme-bound protein, which demonstrates a novel model of heme dependent dimerization. Crystal structures of mutants of ChaN will be determined to probe the role of specific residues in heme-dependent dimerization and in interaction with other Cha transport components. Preliminary crystals of a heme binding domains of Isd proteins have been produced and will be optimized for high-resolution structure determination.