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The Saccharomyces cerevisiae Crs5 Metallothionein metal‐binding abilities and its role in the response to zinc overload
Author(s) -
Pagani Ayelen,
Villarreal Laura,
Capdevila Mercè,
Atrian Sílvia
Publication year - 2007
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2006.05510.x
Subject(s) - metallothionein , biology , saccharomyces cerevisiae , zinc , metalloprotein , metal , zinc finger , biochemistry , divalent , microbiology and biotechnology , biophysics , yeast , enzyme , gene , transcription factor , chemistry , organic chemistry , materials science , metallurgy
Summary Crs5 is a Saccharomyces cerevisiae Metallothionein (MT), non‐homologous to the paradigmatic Cu‐thionein Cup1. Although considered a secondary copper‐resistance agent, we show here that it determines survival under zinc overload in a CUP1 ‐null background. Its overexpression prevents the deleterious effects exhibited by CUP1‐CRS5 ‐null cells when exposed to combined Zn/Cu, as it does the mouse MT1 Zn‐thionein, but not Cup1. The detailed characterization of Crs5 in vivo and in vitro Zn(II)‐, Cd(II)‐ and Cu(I)‐binding abilities fully supports its resemblance to mammalian MTs. Hence, Crs5 exhibits a good divalent metal‐binding ability, yielding homometallic, highly chiral and stable Zn and Cd complexes when expressed in media enriched with these metal ions. In Cu‐supplemented cultures, heterometallic Zn,Cu complexes are recovered, unless aeration is kept to a minimum. These features define a Crs5 dual metal‐binding behaviour that is significantly closer to Zn‐thioneins than to Cu‐thioneins. Protein sequence similarities fully support these findings. Overall, a Crs5 function in global metal cell homeostasis, based on its Zn‐binding features, is glimpsed. The comparative evaluation of Crs5 in the framework of MT functional differentiation and evolution allows its consideration as a representative of the primeval eukaryotic forms that progressively evolved to give rise to the Zn‐thionein lineage.