Molecular characterization of a copper transport protein in S. cerevisiae: an unexpected role for copper in iron transport.
We report the identification and characterization of CTR1, a gene in the yeast S. cerevisiae that encodes a multispanning plasma membrane protein specifically required for high affinity copper transport into the cell. The predicted protein contains a methionine- and serine-rich domain that includes 11 examples of the sequence Met-X2-Met, a motif noted in proteins involved in bacterial copper metabolism. CTR1 mutants and deletion strains have profound deficiency in ferrous iron uptake, thus revealing a requirement for copper in mediating ferrous transport into the cell. Genetic evidence suggests that the target for this requirement is the FET3 gene (detailed in a companion study), predicted to encode a copper-containing protein that acts as a cytosolic ferro-oxidase. These findings provide an unexpected mechanistic link between the uptake of copper and iron.
Dancis
A
A
Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health Bethesda, Maryland 20892.
Yuan
D S
DS
Haile
D
D
Askwith
C
C
Eide
D
D
Moehle
C
C
Kaplan
J
J
Klausner
R D
RD
D000595:Amino Acid Sequence; D001483:Base Sequence; D001692:Biological Transport; D027682:Cation Transport Proteins; D003001:Cloning, Molecular; D003300:Copper / Q000378:metabolism*; D000079923:Copper Transporter 1; D005296:Ferrous Compounds / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D005800:Genes, Fungal; D007501:Iron / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
C490078:CTR1 protein, S cerevisiae; D027682:Cation Transport Proteins; D000079923:Copper Transporter 1; D005296:Ferrous Compounds; D005656:Fungal Proteins; D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; D003300:Copper; D007501:Iron