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.
Biochim Biophys Acta
; 1847(12): 1487-94, 2015 Dec.
Article
em En
| MEDLINE
| ID: mdl-26301481
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Plasmodium falciparum
/
Grupo dos Citocromos b
/
Genética
/
Proteínas Ferro-Enxofre
Limite:
Animals
Idioma:
En
Revista:
Biochim Biophys Acta
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
França