SGD Paper 
Nouet C, et al. (2009) Functional analysis of yeast bcs1 mutants highlights the role of Bcs1p-specific amino acids in the AAA domain. J Mol Biol 388(2):252-61
Abstract: The mitochondrial protein Bcs1p is conserved from Saccharomyces cerevisiae to humans and its C-terminal region exhibits an AAA domain (ATPases Associated with diverse cellular Activities). 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.
| Status: Published | Type: Journal Article | PubMed ID: 19285991 |
Topics addressed in this paper
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| Topics | Genes linked to topics |
|---|---|
| BCS1 | |
| Function/Process |  |
| Genetic Interactions | |
| Mutants/Phenotypes | |
| Primary Literature | |
| Protein Processing/Modification/Regulation | |
| Protein Sequence Features | |
| Protein-protein Interactions | |
| Strains/Constructs | |
