Distinct metal binding configurations in ACE1.
The ACE1 protein of Saccharomyces cerevisiae mediates the metal-induced expression of the CUP1 metallothionein (MT) genes. Curiously, ACE1 resembles the MT protein in the types of metal complexes that form. ACE1 binds Cd(II) and Cu(I) ions in distinct configurations, but only the Cu(I) conformer of ACE1 forms a high-affinity and specific complex with DNA. Cu(I) ions associated with ACE1 are known to assemble in a polymetallic CuI-thiolate cluster that resembles Cu-metallothionein in metal coordination properties [Dameron, C. T., Winge, D. R., George, G. N., Sansone, M., Hu, S., & Hamer, D. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 6127-6131]. In contrast to the Cu(I) nuclearity of 6-7 mol equiv in ACE1 and 7 mol equiv in yeast MT, divalent ions, including Cd(II), Zn(II) and Co(II), bind with a maximal stoichiometry of near 4 mol equiv in ACE1 and 4 mol equiv in yeast MT. Charge-transfer bands consistent with metal:thiolate coordination were observed in CdACE1 and CoACE1. Spectroscopic studies of CoIIACE1 and EXAFS analysis of CdIIACE1 revealed tetrahedral coordination geometry in these complexes. Similar tetrahedral coordination complexes were observed with Co(II) and Cd(II) complexes of MT from S. cerevisiae. Metal binding in ACE1 is clearly similar to that in MT, and therefore the MT-metal clusters appear to be a good structural model of the metal center of ACE1.
Dameron
C T
CT
University of Utah Medical Center, Salt Lake City 84132.
George
G N
GN
Arnold
P
P
Santhanagopalan
V
V
Winge
D R
DR
D017123:Bacteriophage T7 / Q000235:genetics; D001665:Binding Sites; D004271:DNA, Fungal / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000378:metabolism*; D008668:Metallothionein / Q000378:metabolism; D008670:Metals / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D013057:Spectrum Analysis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014965:X-Rays
C060256:CUP2 protein, S cerevisiae; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D008670:Metals; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D008668:Metallothionein