STUDIES OF IRON TRANSPORT AND HOMEOSTASIS; STUDIES OF ARCHAEAL VIRUS

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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.