title: 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.
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.
authors: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, 91198 Gif-sur-Yvette, France.
authors: Zehua
authors: Z
authors: Song
authors: UMR 216, Faculté de Pharmacie de Paris, Université Paris Descartes, and Institut de Recherche pour le Développement, 75006 Paris, France.
authors: Jérôme
authors: J
authors: Clain
authors: Institut de Chimie des Substances Naturelles, CNRS, UPR 2301, Labex LERMIT, 91198 Gif-sur-Yvette, France.
authors: Bogdan I
authors: BI
authors: Iorga
authors: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, 91198 Gif-sur-Yvette, France.
authors: Cindy
authors: C
authors: Vallières
authors: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, 91198 Gif-sur-Yvette, France.
authors: Anaïs
authors: A
authors: Lalève
authors: Plant Research Laboratory, Michigan State University, East Lansing, MI 48824, USA.. Electronic address: nefisher@msu.edu.
authors: Nicholas
authors: N
authors: Fisher
authors: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, 91198 Gif-sur-Yvette, France. Electronic address: meunier@cgm.cnrs-gif.fr.
authors: Brigitte
authors: B
authors: Meunier
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002384:Catalysis; D003573:Cytochrome b Group / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005823:Genetics; D007506:Iron-Sulfur Proteins / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D013481:Superoxides / Q000378:metabolism
chemical_list: D003573:Cytochrome b Group; D007506:Iron-Sulfur Proteins; D013481:Superoxides
keywords: Malaria parasite; Respiratory complex III; Superoxide production; Yeast model