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: 8170096
• 负责人: CHARLES MARTIN LAWRENCE
• 金额: $ 0.27万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8170096
• 关键词: Adaptor Signaling Protein; Age; Anemia; Archaeal Viruses; Bacteria; Bacteriophages; Bacteroides; Bacteroides fragilis; Biochemical Genetics; Cessation of life; Computer Retrieval of Information on Scientific Projects Database; Databases; Disease; Eukaryota; 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).

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它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，遗传性血色素沉着病是已知的最常见的常染色体隐性遗传疾病，在北欧血统的人群中，其携带频率约为十分之一。此外，许多其他铁超载疾病也是已知的，通常会导致 50 岁之前死亡。我们正在进行许多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 Steap 家族。我们还在研究一类新鉴定的 12 个亚基铁蛋白样蛋白，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人类厌氧病原体：脆弱拟杆菌和多形拟杆菌中。第二个项目侧重于古菌病毒的结构研究。已知有超过 5,000 种病毒和噬菌体感染细菌和真核生物，但是，已鉴定出的古细菌病毒不到 35 种，这主要是因为人们才刚刚开始寻找它们。第一个超嗜热天穹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，如果没有直接的生化和遗传学研究，很难确定这些病毒基因的功能。因此，我们正在从事“结构的功能”？该项目重点关注两个超嗜热天穹病毒家族。我们现在已经解决了 8 种穹窿病毒蛋白的结构，并且在每种情况下，这些结构都对这些蛋白的功能提出了具体建议（复制终止蛋白、翼状螺旋和锌指转录因子、糖基转移酶、接头蛋白和假定的假日连接）重组酶）。