Document Detail


A single amino acid change in the yeast vacuolar metal transporters ZRC1 and COT1 alters their substrate specificity.
MedLine Citation:
PMID:  18930916     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Iron is an essential nutrient but in excess may damage cells by generating reactive oxygen species due to Fenton reaction or by substituting for other transition metals in essential proteins. The budding yeast Saccharomyces cerevisiae detoxifies cytosolic iron by storage in the vacuole. Deletion of CCC1, which encodes the vacuolar iron importer, results in high iron sensitivity due to increased cytosolic iron. We selected mutants that permitted Deltaccc1 cells to grow under high iron conditions by UV mutagenesis. We identified a mutation (N44I) in the vacuolar zinc transporter ZRC1 that changed the substrate specificity of the transporter from zinc to iron. COT1, a vacuolar zinc and cobalt transporter, is a homologue of ZRC1 and both are members of the cation diffusion facilitator family. Mutation of the homologous amino acid (N45I) in COT1 results in an increased ability to transport iron and decreased ability to transport cobalt. These mutations are within the second hydrophobic domain of the transporters and show the essential nature of this domain in the specificity of metal transport.
Authors:
Huilan Lin; Attila Kumánovics; Jenifer M Nelson; David E Warner; Diane McVey Ward; Jerry Kaplan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-10-16
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  283     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-12-01     Completed Date:  2009-02-04     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  33865-73     Citation Subset:  IM    
Affiliation:
Department of Pathology, School of Medicine, University of Utah, Salt Lake City, Utah 84132, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Biological Transport
Cation Transport Proteins / genetics,  physiology*
Gene Expression Regulation, Fungal*
Iron / chemistry
Metals / chemistry
Molecular Sequence Data
Mutagenesis
Saccharomyces cerevisiae / genetics,  metabolism*
Saccharomyces cerevisiae Proteins / genetics,  physiology*
Sequence Homology, Amino Acid
Substrate Specificity
Vacuoles / metabolism
Zinc / chemistry
beta-Galactosidase / metabolism
Grant Support
ID/Acronym/Agency:
5P30KD72437//PHS HHS; DK30534/DK/NIDDK NIH HHS; NCI-CCSG P30CA 42014/CA/NCI NIH HHS; T32 DK07115-29/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/COT1 protein, S cerevisiae; 0/Cation Transport Proteins; 0/Metals; 0/Saccharomyces cerevisiae Proteins; 0/ZRC1 protein, S cerevisiae; 7439-89-6/Iron; 7440-66-6/Zinc; EC 3.2.1.23/beta-Galactosidase
Comments/Corrections

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