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Title: | Physiologically relevant reconstitution of iron-sulfur cluster biosynthesis uncovers persulfide- processing functions of ferredoxin-2 and frataxin |
Author: | Gervason, Sylvain Larkem, Djabir Mansour, Amir Ben Botzanowski, Thomas Müller, Christina S. Pecqueur, Ludovic Le Pavec, Gwenaelle Delaunay-Moisan, Agnès Brun Cubero, Omar Agramunt, Jordi Grandas Sagarra, Anna Fontecave, Marc Schünemann, Volker Cianférani, Sarah Sizun, Christina Toledano, Michel B. D'Autréaux, Benoit |
Keywords: | Malalties neurodegeneratives Bioquímica Biosíntesi Proteïnes Neurodegenerative Diseases Biochemistry Biosynthesis Proteins |
Issue Date: | 2019 |
Publisher: | Nature Publishing Group |
Abstract: | Iron-sulfur (Fe-S) clusters are essential protein cofactors whose biosynthetic defects lead to severe diseases among which is Friedreich's ataxia caused by impaired expression of frataxin (FXN). Fe-S clusters are biosynthesized on the scaffold protein ISCU, with cysteine desulfurase NFS1 providing sulfur as persulfide and ferredoxin FDX2 supplying electrons, in a process stimulated by FXN but not clearly understood. Here, we report the breakdown of this process, made possible by removing a zinc ion in ISCU that hinders iron insertion and promotes non-physiological Fe-S cluster synthesis from free sulfide in vitro. By binding zinc-free ISCU, iron drives persulfide uptake from NFS1 and allows persulfide reduction into sulfide by FDX2, thereby coordinating sulfide production with its availability to generate Fe-S clusters. FXN stimulates the whole process by accelerating persulfide transfer. We propose that this reconstitution recapitulates physiological conditions which provides a model for Fe-S cluster biosynthesis, clarifies the roles of FDX2 and FXN and may help develop Friedreich's ataxia therapies. |
Note: | Reproducció del document publicat a: https://doi.org/10.1038/s41467-019-11470-9 |
It is part of: | Nature Communications, 2019, vol. 10, p. 3566 |
URI: | http://hdl.handle.net/2445/140541 |
Related resource: | https://doi.org/10.1038/s41467-019-11470-9 |
ISSN: | 2041-1723 |
Appears in Collections: | Articles publicats en revistes (Química Inorgànica i Orgànica) |
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