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Structural bases for the interaction of frataxin with the central components of iron–sulphur cluster assembly

Prischi, Filippo and Konarev, Petr V and Iannuzzi, Clara and Pastore, Chiara and Adinolfi, Salvatore and Martin, Stephen R and Svergun, Dmitri I and Pastore, Annalisa (2010) 'Structural bases for the interaction of frataxin with the central components of iron–sulphur cluster assembly.' Nature Communications, 1 (1). 95-. ISSN 2041-1723

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Abstract

Reduced levels of frataxin, an essential protein of as yet unknown function, are responsible for causing the neurodegenerative pathology Friedreich's ataxia. Independent reports have linked frataxin to iron-sulphur cluster assembly through interactions with the two central components of this machinery: desulphurase Nfs1/IscS and the scaffold protein Isu/IscU. In this study, we use a combination of biophysical methods to define the structural bases of the interaction of CyaY (the bacterial orthologue of frataxin) with the IscS/IscU complex. We show that CyaY binds IscS as a monomer in a pocket between the active site and the IscS dimer interface. Recognition does not require iron and occurs through electrostatic interactions of complementary charged residues. Mutations at the complex interface affect the rates of enzymatic cluster formation. CyaY binding strengthens the affinity of the IscS/IscU complex. Our data suggest a new paradigm for understanding the role of frataxin as a regulator of IscS functions. © 2010 Macmillan Publishers Limited. All rights reserved.

Item Type: Article
Uncontrolled Keywords: Iron-Binding Proteins; Iron-Sulfur Proteins; Catalytic Domain; Protein Structure, Secondary; Protein Structure, Tertiary; Protein Binding; Mutation; Models, Theoretical
Subjects: Q Science > Q Science (General)
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 04 Feb 2016 11:41
Last Modified: 15 Jan 2022 00:30
URI: http://repository.essex.ac.uk/id/eprint/14838

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