STRUCTURAL STUDIES OF IRON TRANSPORT AND HOMEOSTASIS AND OF ARCHAEAL VIRUSES

铁运输和体内平衡以及古细菌病毒的结构研究

• 批准号: 7722114
• 负责人: CHARLES MARTIN LAWRENCE
• 金额: $ 0.02万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7722114
• 关键词: Adaptor Signaling Protein; Age; Anemia; Archaeal Viruses; Bacteria; Bacteriophages; Bacteroides; Bacteroides fragilis; Biochemical Genetics; Cessation of life; Class; Computer Retrieval of Information on Scientific Projects Database; Databases; Disease; Eukaryota; Eukaryotic Cell; European; Family; Ferritin; Frequencies; Funding; Grant; Hand; Hereditary hemochromatosis; Holidays; Homeostasis; Human; Institution; Iron; Iron Overload; Proteins; Research; Research Personnel; Resources; Source; Structure; Suggestion; Transferrin Receptor; United States National Institutes of Health; Viral Genes; Viral Genome; Viral Proteins; Virus; Winged Helix; Zinc Fingers; glycosyltransferase; iron (III) reductase; numb protein; pathogen; protein function; recombinase; transcription factor

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).

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 一方面，全球超过10亿人患有贫血。另一方面，在北欧提取者中，遗传性血色素沉着症是最普遍的常染色体隐性疾病，其载体频率约为10分之一。此外，许多其他铁超负荷疾病是已知的，通常在50岁时导致死亡。我们从事了许多参与人类铁运输的蛋白质的结构性研究，包括转铁蛋白受体和STEAP的屈服酶家族。我们还研究了新鉴定的12种亚基铁蛋白样蛋白，其中包含定义的？硫代铁蛋白基序？这些蛋白质存在于最常见的厌氧人类病原体中，菌群脆弱的菌根和细菌thetaiotamicron。第二个项目着重于古细菌病毒的结构研究。已知有5,000多个病毒和噬菌体感染细菌和真核生物，但是，已经发现了不到35种古细菌病毒，这主要是因为人们才刚刚开始寻找它们。现在已经对第一个过度疗法的病毒基因组进行了测序，它们通常显示与公共数据库缺乏同源性。因此，没有直接的生化和遗传研究，很难将功能分配给这些病毒基因。因此，我们从结构中从事？侧重于两个高疗法脑乳腺癌病毒的项目。现在，我们已经解决了8种Crenarchaeal病毒蛋白的结构，在每种情况下，结构都对这些蛋白质的功能提出了具体建议（复制终结蛋白，有翼的螺旋和锌指转录因子，糖基转移转移酶，辅助蛋白，衔接蛋白和假期节日连接重物结合酶）。