Document Detail


Effector role reversal during evolution: the case of frataxin in Fe-S cluster biosynthesis.
MedLine Citation:
PMID:  22352884     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Human frataxin (FXN) has been intensively studied since the discovery that the FXN gene is associated with the neurodegenerative disease Friedreich's ataxia. Human FXN is a component of the NFS1-ISD11-ISCU2-FXN (SDUF) core Fe-S assembly complex and activates the cysteine desulfurase and Fe-S cluster biosynthesis reactions. In contrast, the Escherichia coli FXN homologue CyaY inhibits Fe-S cluster biosynthesis. To resolve this discrepancy, enzyme kinetic experiments were performed for the human and E. coli systems in which analogous cysteine desulfurase, Fe-S assembly scaffold, and frataxin components were interchanged. Surprisingly, our results reveal that activation or inhibition by the frataxin homologue is determined by which cysteine desulfurase is present and not by the identity of the frataxin homologue. These data are consistent with a model in which the frataxin-less Fe-S assembly complex exists as a mixture of functional and nonfunctional states, which are stabilized by binding of frataxin homologues. Intriguingly, this appears to be an unusual example in which modifications to an enzyme during evolution inverts or reverses the mode of control imparted by a regulatory molecule.
Authors:
Jennifer Bridwell-Rabb; Clara Iannuzzi; Annalisa Pastore; David P Barondeau
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-03-15
Journal Detail:
Title:  Biochemistry     Volume:  51     ISSN:  1520-4995     ISO Abbreviation:  Biochemistry     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-03-27     Completed Date:  2012-05-14     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2506-14     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Carbon-Sulfur Lyases / metabolism
Escherichia coli
Escherichia coli Proteins / metabolism
Humans
Iron / metabolism*
Iron-Binding Proteins / chemistry,  metabolism*
Iron-Regulatory Proteins / metabolism
Iron-Sulfur Proteins / metabolism
Sequence Homology, Amino Acid
Sulfur / metabolism*
Grant Support
ID/Acronym/Agency:
1R01GM096100/GM/NIGMS NIH HHS; MC_U117584256//Medical Research Council; R01 GM096100-01A1/GM/NIGMS NIH HHS; U117584256//Medical Research Council
Chemical
Reg. No./Substance:
0/CyaY protein, E coli; 0/Escherichia coli Proteins; 0/ISD11 protein, human; 0/Iron-Binding Proteins; 0/Iron-Regulatory Proteins; 0/Iron-Sulfur Proteins; 0/IscU protein, E coli; 0/frataxin; 70FD1KFU70/Sulfur; E1UOL152H7/Iron; EC 4.4.-/Carbon-Sulfur Lyases; EC 4.4.1.-/NFS1 protein, human; EC 4.4.1.-/cysteine desulfurase
Comments/Corrections

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