The DOI matches its Crossref record; 51 of the 53 references it cites were found in a registry or an index.
Towards a structural understanding of Friedreich’s ataxia: the solution structure of frataxin
Open accessAbstract
Background Lesions in the gene for frataxin, a nuclear-encoded mitochondrial protein, cause the recessively inherited condition Friedreich's ataxia. It is thought that the condition arises from disregulation of mitochondrial iron homeostasis, with concomitant oxidative damage leading to neuronal death. Very little is, as yet, known about the biochemical function of frataxin. Results Here, we show that the mature form of recombinant frataxin behaves in solution as a monodisperse species that is composed of a 15-residue-long unstructured N terminus and an evolutionarily conserved C-terminal region that is able to fold independently. The structure of the C-terminal domain consists of a stable seven-stranded antiparallel beta sheet packing against a pair of parallel helices. The structure is compact with neither grooves nor cavities, features that are typical of iron-binding modules. Exposed evolutionarily conserved residues cover a broad area and all cluster on the beta-sheet face of the structure, suggesting that this is a functionally important surface. The effect of two clinically occurring mutations on the fold was checked experimentally. When the mature protein was titrated with iron, no tendency to iron-binding or to aggregation was observed. Conclusions Knowledge of the frataxin structure provides important guidelines as to the nature of the frataxin binding partner. The absence of all the features expected for an iron-binding activity, the large conserved area on its surface and lack of evidence for iron-binding activity strongly support an indirect involvement of frataxin in iron metabolism. The effects of point mutations associated with Friedreich's ataxia can be rationalised by knowledge of the structure and suggest possible models for the occurrence of the disease in compound heterozygous patients.
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“It negatively regulates iron efflux by binding Fpn and triggering its internalization and subsequent degradation (215).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [215]
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“Fpn is posttranslationally regulated by a peptide hormone, hepcidin (215).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [215]
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“Over-expression of Fpn accelerates export of cytosolic iron (215)”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [215]
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Cites
Thompson, J. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.24.4876 · Cited by 38,685
AQUA and PROCHECK-NMR: Programs for checking the quality of protein structures solved by NMR
Laskowski, R., Rullmann, J. A., MacArthur, M., Kaptein, R., & Thornton, J. (1996) · Journal of Biomolecular NMR · doi:10.1007/bf00228148 · Cited by 5,502
WHAT IF: A molecular modeling and drug design program
Vriend, G. (1990) · Journal of Molecular Graphics · doi:10.1016/0263-7855(90)80070-v · Cited by 3,476
Friedreich's Ataxia: Autosomal Recessive Disease Caused by an Intronic GAA Triplet Repeat Expansion
Campuzano, V., Montermini, L., Moltò, M. D., Pianese, L., Cossée, M., Cavalcanti, F., Monros, E., Rodius, F., Duclos, F., Monticelli, A., et al. (1996) · Science · doi:10.1126/science.271.5254.1423 · Cited by 2,786
Torsion angle dynamics for NMR structure calculation with the new program Dyana
Güntert, P., Mumenthaler, C., & Kurt Wüthrich, A. (1997) · Journal of Molecular Biology · doi:10.1006/jmbi.1997.1284 · Cited by 2,781
The ferritins: molecular properties, iron storage function and cellular regulation
Harrison, P. M., & Arosio, P. (1996) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(96)00022-9 · Cited by 2,667
Recognition of errors in three‐dimensional structures of proteins
Sippl, M. J. (1993) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.340170404 · Cited by 2,156
Clinical and Genetic Abnormalities in Patients with Friedreich's Ataxia
Dürr, A., Cossee, M., Agid, Y., Campuzano, V., Mignard, C., Penet, C., Mandel, J.-L., Brice, A., & Koenig, M. (1996) · New England Journal of Medicine · doi:10.1056/nejm199610173351601 · Cited by 1,071
Aconitase and mitochondrial iron–sulphur protein deficiency in Friedreich ataxia
Rötig, A., de Lonlay, P., Chretien, D., Foury, F., Koenig, M., Sidi, D., Munnich, A., & Rustin, P. (1997) · Nature Genetics · doi:10.1038/ng1097-215 · Cited by 991
Regulation of Mitochondrial Iron Accumulation by Yfh1p, a Putative Homolog of Frataxin
Babcock, M., de Silva, D., Oaks, R., Davis-Kaplan, S., Jiralerspong, S., Montermini, L., Pandolfo, M., & Kaplan, J. (1997) · Science · doi:10.1126/science.276.5319.1709 · Cited by 921
Cited by
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Chemistry and biology of eukaryotic iron metabolism
Aisen, P. (2001) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/s1357-2725(01)00063-2 · Cited by 804
“A solution NMR study of human frataxin showed neither grooves nor cavities expected of iron-binding molecules, nor evidence of iron-binding activity by titration with Fe [137].”
BackgroundPuccio, H., Simon, D., Cossée, M., Criqui-Filipe, P., Tiziano, F., Melki, J., Hindelang, C., Matyas, R., Rustin, P., & Koenig, M. (2001) · Nature Genetics · doi:10.1038/84818 · Cited by 738
“Whether frataxin directly binds iron is currently controversia”
BackgroundIntracellular iron transport and storage: from molecular mechanisms to health implications
Mackenzie, E. L., Iwasaki, K., & Tsuji, Y. (2008) · Antioxidants & Redox Signaling · doi:10.1089/ars.2007.1893 · Cited by 526
“In human mature frataxin, the structure is compact, with no signature of iron binding or oligomerization in the presence of iron (212), whereas the mature human frataxin was reported to assemble in (cid:5) 600-kDa homopolymers and bind (cid:2) 10 atoms of iron per frataxin oligomer (44).”
Yoon, T., & Cowan, J. A. (2003) · Journal of the American Chemical Society · doi:10.1021/ja027967i · Cited by 353
The yeast frataxin homolog Yfh1p plays a specific role in the maturation of cellular Fe/S proteins
Mühlenhoff, U. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.17.2025 · Cited by 326
Metadata
- Authors
- Musco, G., Stier, G., Kolmerer, B., Adinolfi, S., Martin, S., Frenkiel, T., Gibson, T., & Pastore, A.
- Affiliations
- European Molecular Biology Laboratory (DE)
- Corresponding author
- Pastore, Annalisa
- Venue
- Structure
- Publisher
- Elsevier BV
- Published
- 2000-07
- Volume
- 8
- Issue
- 7
- Pages
- 695-707
- ISSN
- 0969-2126 (ISSN-L)
- OpenAlex
- W2043666185
- Cited by
- 166
- References
- 53
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 3 · 2023: 5 · 2022: 9 · 2021: 4 · 2020: 4 · 2019: 4 · 2018: 6 · 2017: 3 · 2016: 3 · 2015: 6 · 2014: 11 · 2013: 9 · 2012: 3
- FWCI
- 3.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Structure (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Max Planck Digital Library (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Scuola Normale Superiore di Pisa (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
- Keywords
- Friedreich's ataxia, frataxin, protein solution structure, mitochondrial iron homeostasis, C-terminal domain, antiparallel beta-sheet, point mutations, compound heterozygosity, protein aggregation
- MeSH terms
- Frataxin, Amino Acid Sequence, Animals, Bacterial Proteins, Carrier Proteins, Circular Dichroism, Friedreich Ataxia, Fungal Proteins, Heterozygote, Humans, Iron, Ligands, Mitochondria, Models, Molecular, Molecular Sequence Data, Plant Proteins, Protein Conformation, Recombinant Fusion Proteins, Species Specificity, Structure-Activity Relationship, Helminth Proteins, Sequence Alignment, Point Mutation, Sequence Homology, Amino Acid, Protein Structure, Secondary, Phosphotransferases (Alcohol Group Acceptor), Oxidative Stress, Evolution, Molecular, Iron-Binding Proteins, Transferrin-Binding Proteins, Mice
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