Yeast Frataxin Solution Structure, Iron Binding, and Ferrochelatase Interaction
The mitochondrial protein frataxin is essential for cellular regulation of iron homeostasis. Although the exact function of frataxin is not yet clear, recent reports indicate the protein binds iron and can act as a mitochondrial iron chaperone to transport Fe(II) to ferrochelatase and ISU proteins w...
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Published in | Biochemistry (Easton) Vol. 43; no. 51; pp. 16254 - 16262 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Chemical Society
28.12.2004
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Subjects | |
Online Access | Get full text |
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Summary: | The mitochondrial protein frataxin is essential for cellular regulation of iron homeostasis. Although the exact function of frataxin is not yet clear, recent reports indicate the protein binds iron and can act as a mitochondrial iron chaperone to transport Fe(II) to ferrochelatase and ISU proteins within the heme and iron−sulfur cluster biosynthetic pathways, respectively. We have determined the solution structure of apo yeast frataxin to provide a structural basis of how frataxin binds and donates iron to the ferrochelatase. While the protein's α−β-sandwich structural motif is similar to that observed for human and bacterial frataxins, the yeast structure presented in this report includes the full N-terminus observed for the mature processed protein found within the mitochondrion. In addition, NMR spectroscopy was used to identify frataxin amino acids that are perturbed by the presence of iron. Conserved acidic residues in the helix 1−strand 1 protein region undergo amide chemical shift changes in the presence of Fe(II), indicating a possible iron-binding site on frataxin. NMR spectroscopy was further used to identify the intermolecular binding interface between ferrochelatase and frataxin. Ferrochelatase appears to bind to frataxin's helical plane in a manner that includes its iron-binding interface. |
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Bibliography: | NMR assignments, atomic coordinates, and chemical shift data for frataxin have been deposited (PDB entry 1XAQ, BMRB entry 11688). This work is supported by the American Heart Association, Midwest Affiliate (Grant 0130527Z to T.L.S.) and by the National Institutes of Health (Grant DK53953 to A.D.). ark:/67375/TPS-HG1LN2ZL-G istex:6B6F195A97FECB152B0D0807957D302B0EFB505C ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0006-2960 1520-4995 |
DOI: | 10.1021/bi0488193 |