title: The Candida albicans CTR1 gene encodes a functional copper transporter.
abstract: Copper and iron uptake in Saccharomyces cerevisiae are linked through a high-affinity ferric/cupric-reductive uptake system. Evidence suggests that a similar system operates in Candida albicans. The authors have identified a C. albicans gene that is able to rescue a S. cerevisiae ctr1/ctr3-null mutant defective in high-affinity copper uptake. The 756 bp ORF, designated CaCTR1, encodes a 251 amino acid protein with a molecular mass of 27.8 kDa. Comparisons between the deduced amino acid sequence of the C. albicans Ctr1p and S. cerevisiae Ctr1p indicated that they share 39.6 % similarity and 33.0 % identity over their entire length. Within the predicted protein product of CaCTR1 there are putative transmembrane regions and sequences that resemble copper-binding motifs. The promoter region of CaCTR1 contains four sequences with significant identity to S. cerevisiae copper response elements. CaCTR1 is transcriptionally regulated in S. cerevisiae in response to copper availability by the copper-sensing transactivator Mac1p. Transcription of CaCTR1 in C. albicans is also regulated in a copper-responsive manner. This raises the possibility that CaCTR1 may be regulated in C. albicans by a Mac1p-like transactivator. A C. albicans ctr1-null mutant displays phenotypes consistent with the lack of copper uptake including growth defects in low-copper and low-iron conditions, a respiratory deficiency and sensitivity to oxidative stress. Furthermore, changes in morphology were observed in the C. albicans ctr1-null mutant. It is proposed that CaCTR1 facilitates transport of copper into the cell.
authors.affiliation: Department of Genetics, University of Leicester, Leicester LE1 7RH, UK.
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Marvin
authors.affiliation: Department of Microbiology and Immunology, University of Leicester, Leicester LE1 7RH, UK.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Williams
authors.affiliation: Department of Genetics, University of Leicester, Leicester LE1 7RH, UK.
authors.forename: Annette M
authors.initials: AM
authors.lastname: Cashmore
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002176:Candida albicans / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D027682:Cation Transport Proteins; D003300:Copper / Q000378:metabolism*; D000079923:Copper Transporter 1; D003470:Culture Media; D004271:DNA, Fungal / Q000235:genetics; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D005800:Genes, Fungal; D007501:Iron / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D011401:Promoter Regions, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D013045:Species Specificity; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C490078:CTR1 protein, S cerevisiae; D027682:Cation Transport Proteins; D000079923:Copper Transporter 1; D003470:Culture Media; D004271:DNA, Fungal; D005656:Fungal Proteins; C084954:MAC1 protein, S cerevisiae; D008565:Membrane Proteins; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D003300:Copper; D007501:Iron