STUDIES OF IRON TRANSPORT AND HOMEOSTASIS; STUDIES OF ARCHAEAL VIRUS

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(缺铁)。另一方面，遗传性血色沉着症(铁超载)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十分之一。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。我们从事一些蛋白质的结构研究，这些蛋白质涉及哺乳动物的铁运输和动态平衡。其中一些蛋白质在嗜热生物中有同源蛋白，因此我们还开展了对Sulfolobus solfararicus中铁运输的结构研究。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。第一批古生菌基因组现在已经测序，它们通常显示出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。在两个案例中，我们已经证明了这些病毒蛋白的结构可以暗示功能，我们现在从事的是一项小规模的结构蛋白质组学工作，重点是几个隐古病毒家族的类型病毒。这将有助于勾勒出来自生命树上这第三个分支的病毒的病毒生命周期，并可能确定在生物技术中具有潜在用途的耐热酶。

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 (iron deprivation). On the other, hereditary hemochromatosis (iron overload) 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 mammalian iron transport and homeostasis. Some of these proteins have homologues in thermophilic organisms, thus we have also undertaken structural studies of iron transport in Sulfolobus solfataricus. 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 Archaeal 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. In two cases, we have demonstrated that the structures of these viral proteins can suggest function, and we are now engaged in a small scale structural proteomics effort focused on the type viruses of several crenarchaeal virus families. This will help to sketch in the viral life cycles for the viruses from this third branch in the tree of life, and may also identify thermostable enzymes with potential uses in biotechnology.