STRUCTURAL STUDIES OF IRON TRANSPORT AND HOMEOSTASIS AND OF ARCHAEAL VIRUSES

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。 一方面，全世界有10多亿人患有贫血。另一方面，遗传性血色沉着症是已知的最常见的常染色体隐性遗传病，在北欧血统的人中携带率约为1/10。此外，铁超载的许多其他疾病也是已知的，通常会导致50岁前死亡。我们致力于一些与人类铁转运有关的蛋白质的结构研究，包括转铁蛋白受体和Steap铁还原酶家族。我们还在研究一类新发现的12亚单位铁蛋白样蛋白，它们包含一个决定性的硫代铁蛋白基序？这些蛋白质存在于人类最常见的厌氧病原体--脆弱类杆菌和泰特米隆类杆菌中。第二个项目的重点是古生菌病毒的结构研究。已知的感染细菌和真核生物的病毒和噬菌体有5000多种，然而，目前发现的古生菌病毒不到35种，主要是因为人们才刚刚开始寻找它们。第一批嗜热隐翅虫病毒基因组现已完成测序，它们通常与公共数据库缺乏同源性。因此，如果没有直接的生物化学和遗传学研究，就很难为这些病毒基因分配功能。因此，我们从事的是从结构到功能的工作。该项目的重点是两类嗜热隐翅虫病毒。我们现在已经解决了8种隐古病毒蛋白的结构，每种情况下的结构都对这些蛋白的功能提出了具体的建议(复制终止子蛋白、有翼螺旋和锌指转录因子、糖基转移酶、接头蛋白和可能的假日连接重组酶)。

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. On one hand, more than 1 BILLION people world-wide suffer from anemia. On the other, hereditary hemochromatosis is the most prevalent autosomal recessive disease known with a carrier frequency of approximately 1 in 10, in people of northern European extraction. In addition, many other diseases of iron overload are known, often leading to death by age 50. We are engaged in structural studies of a number of proteins involved in human iron transport, including the transferrin receptor and the Steap family of ferrireductases. We are also studying a newly identified class of 12 subunit ferritin-like proteins that contain a defining ?thioferritin motif?. These proteins are present in the most common anaerobic human pathogens, Bacteroides fragilis and Bacteroides thetaiotamicron. A second project focuses on structural studies of Archaeal viruses. More than 5,000 viruses and phage are known that infect bacteria and the eukaryotes, however, less than 35 Archaeal viruses have been identified, primarily because people are just beginning to look for them. The first hyperthermophilic crenarchaeal viral genomes have now been sequenced, and they generally show a lack of homology with the public databases. Thus it is difficult to assign function to these viral genes without direct biochemical and genetic studies. We are thus engaged in a ?function from structure? project that focuses on two families of hyperthermophilic crenarchaeal viruses. We have now solved structures for 8 crenarchaeal viral proteins, and in each case the structures have made specific suggestions regarding the functions of these proteins (replication terminator proteins, winged helix and zinc finger transcription factors, a glycosyltransferase, adaptor proteins and a putative holiday junction recombinase).