The complex multiprotein systems for the assembly of protein-bound iron–sulfur (Fe–S) clusters are well defined in Gram-negative model organisms. However, little is known about Fe–S cluster biogenesis in other bacterial species. The ISC (iron–sulfur cluster) operon of Mycobacterium tuberculosis lacks several genes known to be essential for the function of this system in other organisms. However, the cysteine desulfurase IscSMtb (Rv number Rv3025c; Mtb denotes M. tuberculosis) is conserved in this important pathogen. The present study demonstrates that deleting iscSMtb renders the cells microaerophilic and hypersensitive to oxidative stress. Moreover, the ∆iscSMtb mutant shows impaired Fe–S cluster-dependent enzyme activity, clearly indicating that IscSMtb is associated with Fe–S cluster assembly. An extensive interaction network of IscSMtb with Fe–S proteins was identified, suggesting a novel mechanism of sulfur transfer by direct interaction with apoproteins. Interestingly, the highly homologous IscS of Escherichia coli failed to complement the ∆iscSMtb mutant and showed a less diverse protein-interaction profile. To identify a structural basis for these observations we determined the crystal structure of IscSMtb, which mirrors adaptations made in response to an ISC operon devoid of IscU-like Fe–S cluster scaffold proteins. We conclude that in M. tuberculosis IscS has been redesigned during evolution to compensate for the deletion of large parts of the ISC operon.
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Research Article|
April 11 2014
The cysteine desulfurase IscS of Mycobacterium tuberculosis is involved in iron–sulfur cluster biogenesis and oxidative stress defence
Jan Rybniker;
Jan Rybniker
1
*Global Health Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
†1st Department of Internal Medicine, University of Cologne, D-50937 Cologne, Germany
1To whom correspondence should be addressed (email jan.rybniker@epfl.ch).
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Florence Pojer;
Florence Pojer
*Global Health Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
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Jan Marienhagen;
Jan Marienhagen
‡Institut für Bio- und Geowissenschaften, IBG-1: Biotechnologie, Forschungszentrum Jülich GmbH, D-52425 Jülich, Germany
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Gaëlle S. Kolly;
Gaëlle S. Kolly
*Global Health Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
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Jeffrey M. Chen;
Jeffrey M. Chen
*Global Health Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
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Edeltraud van Gumpel;
Edeltraud van Gumpel
†1st Department of Internal Medicine, University of Cologne, D-50937 Cologne, Germany
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Pia Hartmann;
Pia Hartmann
†1st Department of Internal Medicine, University of Cologne, D-50937 Cologne, Germany
§Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, D-50937 Cologne, Germany
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Stewart T. Cole
Stewart T. Cole
*Global Health Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
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Publisher: Portland Press Ltd
Received:
June 25 2013
Revision Received:
January 20 2014
Accepted:
February 19 2014
Accepted Manuscript online:
February 19 2014
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2014 Biochemical Society
2014
Biochem J (2014) 459 (3): 467–478.
Article history
Received:
June 25 2013
Revision Received:
January 20 2014
Accepted:
February 19 2014
Accepted Manuscript online:
February 19 2014
Citation
Jan Rybniker, Florence Pojer, Jan Marienhagen, Gaëlle S. Kolly, Jeffrey M. Chen, Edeltraud van Gumpel, Pia Hartmann, Stewart T. Cole; The cysteine desulfurase IscS of Mycobacterium tuberculosis is involved in iron–sulfur cluster biogenesis and oxidative stress defence. Biochem J 1 May 2014; 459 (3): 467–478. doi: https://doi.org/10.1042/BJ20130732
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