Frataxin binds iron

Stable Identifier
R-HSA-1362416
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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Frataxin (FXN) specifically binds 2 atoms of ferrous iron per monomer (reviewed in Stemmler et al. 2010). Iron bound to Frataxin may (Yoon and Cowan 2003, Gerber et al. 2003) or may not (Schmucker et al. 2011) enhance the interaction of Frataxin with NFS1, ICSU, and ISD11. Frataxin was shown to stimulate the cysteine desulfurase activity of NFS1 and was proposed to be a regulator of sulfur production (Tsai et al. 2010). The formation of sulfide by NFS1 is most efficiently observed when NFS1 is in complex with ISD11, ISCU, and FXN in the presence of cysteine and iron. This means that only the complete system of NFS1, ISD11, ISCU, FXN, cysteine, and iron is fully active as a desulfurase. FXN therefore seems to be a regulator of the cysteine desulfurase permitting sulfide production only when all components needed for Fe-S cluster synthesis are present and the ISCU-bound Fe-S cluster can be formed.

Literature References
PubMed ID Title Journal Year
21776984 Structure-function analysis of Friedreich's ataxia mutants reveals determinants of frataxin binding and activation of the Fe-S assembly complex

Bridwell-Rabb, J, Winn, AM, Barondeau, DP

Biochemistry 2011
12785837 Iron-sulfur cluster biosynthesis. Characterization of frataxin as an iron donor for assembly of [2Fe-2S] clusters in ISU-type proteins

Yoon, T, Cowan, JA

J Am Chem Soc 2003
21298097 Mammalian frataxin: an essential function for cellular viability through an interaction with a preformed ISCU/NFS1/ISD11 iron-sulfur assembly complex

Schmucker, S, Martelli, A, Colin, F, Page, A, Wattenhofer-Donzé, M, Reutenauer, L, Puccio, H

PLoS One 2011
11823441 Assembly and iron-binding properties of human frataxin, the protein deficient in Friedreich ataxia

Cavadini, P, O'Neill, HA, Benada, O, Isaya, G

Hum Mol Genet 2002
20873749 Human frataxin is an allosteric switch that activates the Fe-S cluster biosynthetic complex

Tsai, CL, Barondeau, DP

Biochemistry 2010
20522547 Frataxin and mitochondrial FeS cluster biogenesis

Stemmler, TL, Lesuisse, E, Pain, D, Dancis, A

J Biol Chem 2010
18425540 Mapping iron binding sites on human frataxin: implications for cluster assembly on the ISU Fe-S cluster scaffold protein

Huang, J, Dizin, E, Cowan, JA

J Biol Inorg Chem 2008
15509595 Iron-sulfur protein maturation in human cells: evidence for a function of frataxin

Stehling, O, Elsässer, HP, Brückel, B, Mühlenhoff, U, Lill, R

Hum. Mol. Genet. 2004
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