Reference : Functional analysis of yeast bcs1 mutants highlights the role of Bcs1p-specific amino...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Functional analysis of yeast bcs1 mutants highlights the role of Bcs1p-specific amino acids in the AAA domain.
Nouet, Cécile mailto [Université de Liège - ULiège > Département des sciences de la vie > Génomique fonctionnelle et imagerie moléculaire végétale >]
Truan, Gilles [> > > >]
Mathieu, Lise [> > > >]
Dujardin, Genevieve [ > > ]
Journal of Molecular Biology
Academic Press
Yes (verified by ORBi)
United Kingdom
[en] Adenosine Triphosphatases ; Amino Acids ; Binding Sites ; Conserved Sequence ; Electron Transport Complex III ; Humans ; Membrane Proteins/genetics/physiology ; Mitochondrial Proteins/genetics/physiology ; Molecular Chaperones/genetics/physiology ; Mutant Proteins ; Point Mutation ; Protein Structure, Tertiary ; Saccharomyces cerevisiae Proteins/genetics/physiology
[en] The mitochondrial protein Bcs1p is conserved from Saccharomyces cerevisiae to humans and its C-terminal region exhibits an AAA (ATPases associated with diverse cellular activities) domain. The absence of the yeast Bcs1p leads to an assembly defect of the iron-sulfur protein (ISP) subunit within the mitochondrial respiratory complex III, whereas human point mutations located all along the protein cause various pathologies. We have performed a structure-function analysis of the yeast Bcs1p by randomly generating a collection of respiratory-deficient point mutants. We showed that most mutations are in the C-terminal region of Bcs1p and have localized them on a theoretical three-dimensional model based on the structure of several AAA proteins. The mutations can be grouped into classes according to their respiratory competence and their location on the three-dimensional model. We have further characterized five mutants, each substituting an amino acid conserved in yeast and mammalian Bcs1 proteins but not in other AAA proteins. The effects on respiratory complex assembly and Bcs1p accumulation were analyzed. Intragenic and extragenic compensatory mutations able to restore complex III assembly to the mutants affecting the AAA domain were isolated. Our results bring new insights into the role of specific residues in critical regions that are also conserved in the human Bcs1p. We show that (1) residues located at the junction between the Bcs1p-specific and the AAA domains are important for the activity and stability of the protein and (2) the residue F342 is important for interactions with other partners or substrate proteins.

File(s) associated to this reference

Fulltext file(s):

Open access
Nouet et al 2009.docAuthor postprint1.17 MBView/Open

Bookmark and Share SFX Query

All documents in ORBi are protected by a user license.