Document Detail


Frataxin interacts with Isu1 through a conserved tryptophan in its beta-sheet.
MedLine Citation:
PMID:  19884169     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Friedreich's ataxia is a neurodegenerative disease caused by the low expression of frataxin, a mitochondrial iron-binding protein which plays an important, but non-essential, role in the formation of iron-sulfur (Fe/S) clusters. It has been shown that Yfh1, the yeast frataxin homologue, interacts functionally and physically with Isu1, the scaffold protein on which the Fe/S clusters are assembled. The large beta-sheet platform of frataxin is a good ligand candidate for this interaction. We have generated 12 yeast mutants in conserved residues of the beta-sheet protruding at the surface or buried in the protein core. The Q129A, I130A, W131A(F) and R141A mutations, which reside in surface exposed residues of the fourth and fifth beta-strands, result in severe cell growth inhibition on high-iron media and low aconitase activity, indicating that Fe/S cluster biosynthesis is impaired. The null phenotype of the I130A mutant results from the high instability of the protein, pointing that this buried residue is essential for folding. In contrast, Gln-129, Trp-131 and Arg-141 residues which are spatially closely clustered define a patch important for protein function. Co-immunoprecipitation experiments using cell extracts show that W131A, unlike W131F, is the sole mutation that strongly decreases the interaction with Isu1. Therefore, Trp-131, which is the only strictly conserved frataxin residue in all sequenced species, appears as a major contributor to the interaction with Isu1 through its surface-exposed aromatic side chain.
Authors:
S?bastien Leidgens; S?bastien De Smet; Fran?oise Foury
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-11-02
Journal Detail:
Title:  Human molecular genetics     Volume:  19     ISSN:  1460-2083     ISO Abbreviation:  Hum. Mol. Genet.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2009-12-23     Completed Date:  2010-03-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9208958     Medline TA:  Hum Mol Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  276-86     Citation Subset:  IM    
Affiliation:
Unit? de Biochimie Physiologique, Institut des Sciences de la Vie, Universit? Catholique de Louvain, Louvain-la-Neuve, Belgium.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Conserved Sequence
Friedreich Ataxia / genetics,  metabolism*
Humans
Iron-Binding Proteins / chemistry*,  genetics,  metabolism*
Mitochondrial Proteins / genetics,  metabolism*
Models, Biological
Molecular Conformation
Molecular Sequence Data
Protein Binding
Protein Structure, Secondary
Saccharomyces cerevisiae / chemistry,  genetics,  metabolism*
Saccharomyces cerevisiae Proteins / genetics,  metabolism*
Sequence Alignment
Tryptophan / chemistry*,  genetics,  metabolism
Chemical
Reg. No./Substance:
0/ISU1 protein, S cerevisiae; 0/Iron-Binding Proteins; 0/Mitochondrial Proteins; 0/Saccharomyces cerevisiae Proteins; 0/frataxin; 73-22-3/Tryptophan

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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