STUDIES OF IRON TRANSPORT AND HOMEOSTASIS; STUDIES OF ARCHAEAL VIRUS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。一方面，全世界有超过10亿人患有贫血（缺铁）。另一方面，遗传性血色素沉着症（铁超载）是已知的最普遍的常染色体隐性遗传病，携带者频率约为十分之一，在北欧提取的人群中。此外，已知还有许多其他由铁超载引起的疾病，通常会导致50岁死亡。我们从事一些涉及哺乳动物铁转运和体内平衡的蛋白质的结构研究。其中一些蛋白质在嗜热生物中有同源物，因此我们也进行了硫虫铁转运的结构研究。第二个项目侧重于古细菌病毒的结构研究。已知有5000多种病毒和噬菌体可以感染细菌和真核生物，然而，发现的古细菌病毒还不到35种，这主要是因为人们刚刚开始寻找它们。第一批古细菌基因组现在已经测序，它们普遍显示与公共数据库缺乏同源性。因此，如果没有直接的生化和遗传学研究，很难确定这些病毒基因的功能。在两种情况下，我们已经证明了这些病毒蛋白的结构可以提示功能，我们现在正在进行一项小规模的结构蛋白质组学研究，重点研究几种creusal病毒家族的病毒类型。这将有助于勾画出来自生命之树第三分支的病毒的生命周期，也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.