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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 一方面，全世界有超过10亿人患有贫血症。另一方面，遗传性血色病是最常见的常染色体隐性遗传病，在北方欧洲血统的人群中，其携带者频率约为1/10。此外，已知许多其他铁过载疾病，通常导致50岁之前死亡。我们正在从事一些参与人体铁转运的蛋白质的结构研究，包括转铁蛋白受体和铁还原酶的Steap家族。我们还研究了一类新发现的12亚基铁蛋白样蛋白，包含一个定义？硫铁蛋白基序？这些蛋白质存在于最常见的厌氧人类病原体脆弱拟杆菌和多形拟杆菌中。第二个项目的重点是肠道病毒的结构研究。已知有超过5,000种病毒和噬菌体感染细菌和真核生物，然而，只有不到35种病毒被鉴定出来，主要是因为人们才刚刚开始寻找它们。第一个超嗜热泉古菌病毒基因组现已测序，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，很难确定这些病毒基因的功能。我们就这样参与了一场？从结构功能？该项目的重点是两个家庭的超嗜热crenarchaeal病毒。我们现在已经解决了8 crenarchaeal病毒蛋白的结构，并在每种情况下的结构作出了具体的建议，这些蛋白质的功能（复制终止子蛋白，翅螺旋和锌指转录因子，糖基转移酶，衔接蛋白和推定的假期连接重组酶）。

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).