Interplay between the hinge region of iron sulphur protein and the Qo site in the bc1 complex — Analysis of Plasmodium-like mutations in the yeast enzyme - Archive ouverte HAL
Article Dans Une Revue Biochimica biophysica acta (BBA) - Bioenergetics Année : 2015

Interplay between the hinge region of iron sulphur protein and the Qo site in the bc1 complex — Analysis of Plasmodium-like mutations in the yeast enzyme

Résumé

The respiratory chain bc1 complex is central to mitochondrial bioenergetics and the target of antiprotozoals. We characterized a modified yeast bc1 complex that more closely resemble Plasmodium falciparum enzyme. The mutant version was generated by replacing ten cytochrome b Qo site residues by P. falciparum equivalents. The Plasmodium-like changes caused a major dysfunction of the catalytic mechanism of the bc1 complex resulting in superoxide overproduction and respiratory growth defect. The defect was corrected by substitution of the conserved residue Y279 by a phenylalanine, or by mutations in or in the vicinity of the hinge domain of the iron–sulphur protein. It thus appears that side-reactions can be prevented by the substitution Y279F or the modification of the iron–sulphur protein hinge region. Interestingly, P. falciparum — and all the apicomplexan — contains an unusual hinge region. We replaced the yeast hinge region by the Plasmodium version and combined it with the Plasmodium-like version of the Qo site. This combination restored the respiratory growth competence. It could be suggested that, in the apicomplexan, the hinge region and the cytochrome b Qo site have co-evolved to maintain catalytic efficiency of the bc1 complex Qo site.

Dates et versions

hal-01402828 , version 1 (25-11-2016)

Identifiants

Citer

Zehua Song, Jérôme Clain, Bogdan I. Iorga, Cindy Vallières, Anaïs Lalève, et al.. Interplay between the hinge region of iron sulphur protein and the Qo site in the bc1 complex — Analysis of Plasmodium-like mutations in the yeast enzyme. Biochimica biophysica acta (BBA) - Bioenergetics, 2015, 1847 (12), pp.1487 - 1494. ⟨10.1016/j.bbabio.2015.08.005⟩. ⟨hal-01402828⟩
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