Title:
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Physiologically relevant reconstitution of iron-sulfur cluster biosynthesis uncovers persulfide- processing functions of ferredoxin-2 and frataxin
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Author:
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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 Segarra, Anna; Fontecave, Marc; Schünemann, Volker; Cianférani, Sarah; Sizun, Christina; Tolédano, Michel B.; D'Autréaux, Benoit
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Other authors:
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Universitat de Barcelona |
Abstract:
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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. |
Subject(s):
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-Malalties neurodegeneratives -Bioquímica -Biosíntesi -Proteïnes -Neurodegenerative Diseases -Biochemistry -Biosynthesis -Proteins |
Rights:
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cc-by (c) Gervason, Sylvain et al., 2019
http://creativecommons.org/licenses/by/3.0/es |
Document type:
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Article Article - Published version |
Published by:
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Nature Publishing Group
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