Structure-Function Study of Cellular Iron Chemistry
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The Ohio State University / OhioLINK
2009
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| Online Access: | http://rave.ohiolink.edu/etdc/view?acc_num=osu1245414801 |
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ndltd-OhioLink-oai-etd.ohiolink.edu-osu12454148012021-08-03T05:56:35Z Structure-Function Study of Cellular Iron Chemistry Huang, Jia Chemistry Iron-Sulfur Cluster Frataxin Human ISU IRP1 HscB ITC <p>Iron-sulfur clusters are small inorganic cofactors found in all kingdoms of life. The iron-sulfur cluster biogenesis is a complex system which involves a surprisingly large group of proteins. In human cells, frataxin is believed to recruit ferrous iron from the labile iron pool and subsequently deliver it to the scaffold protein human ISU where the iron-sulfur clusters will form. Deficiency in cellular frataxin production results in a human disease, Friedreich's ataxia which affects 1 in 50,000 humans. By using mutagenesis, the activities of frataxin mutants were investigated. We found that frataxin may have a pool of potential sites that can stably bind an iron center when bridged to a variety of physiological targets; there may not be unique binding loci, but rather a number of locations that provide flexibility in the binding of physiological partner proteins. </p><p>Frataxin has been found to repair the damaged cluster on mitochondrial aconitase. We herein investigated its functional role towards cytosolic aconitase, IRP1, which can register the iron level and is important for the iron homeostasis of human cells. Frataxin can bind to cytosolic aconitase and repair the damaged clusters ([3Fe-4S]) into [4Fe-4S] clusters.</p><p> We reported the cloning and overexpression of human mitochondrial HscB, a J-type co-chaperone, and demonstrated an interaction between human frataxin and human HscB by cross-linking experiments and ITC. HscB was also shown to promote cleavage of the N-terminal domain of full-length human frataxin. </p><p>Human ISU protein contains three highly conserved cysteine residues (C44, C70, and C113) that mutagenesis studies suggested to be directly coordinated to the cluster. The fourth ligand is still unclear. H112 was mutated into alanine or aspartate, and the effects of the mutation were evaluated. We found that H112 might be the fourth ligand that helps to stabilize the cluster, however, it was not absolutely needed for the formation of cluster; it might be the ligand that helps to deliver iron.</p> 2009-09-10 English text The Ohio State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=osu1245414801 http://rave.ohiolink.edu/etdc/view?acc_num=osu1245414801 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
| collection |
NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
Chemistry Iron-Sulfur Cluster Frataxin Human ISU IRP1 HscB ITC |
| spellingShingle |
Chemistry Iron-Sulfur Cluster Frataxin Human ISU IRP1 HscB ITC Huang, Jia Structure-Function Study of Cellular Iron Chemistry |
| author |
Huang, Jia |
| author_facet |
Huang, Jia |
| author_sort |
Huang, Jia |
| title |
Structure-Function Study of Cellular Iron Chemistry |
| title_short |
Structure-Function Study of Cellular Iron Chemistry |
| title_full |
Structure-Function Study of Cellular Iron Chemistry |
| title_fullStr |
Structure-Function Study of Cellular Iron Chemistry |
| title_full_unstemmed |
Structure-Function Study of Cellular Iron Chemistry |
| title_sort |
structure-function study of cellular iron chemistry |
| publisher |
The Ohio State University / OhioLINK |
| publishDate |
2009 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=osu1245414801 |
| work_keys_str_mv |
AT huangjia structurefunctionstudyofcellularironchemistry |
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1719428179372802048 |