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Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The yeast transcriptional activator Zap1 contains two uncommon structural motifs designated zinc finger pair domains. The hallmark of this domain is the packing of two zinc finger motifs in one globular unit. One finger pair domain in Zap1 contains the AD2 transactivation domain. Zn(II) binding to this domain (ZF1/2) is kinetically labile yielding a zinc-regulated transactivator. The second finger pair domain (ZF3/4) lies within the DNA-binding domain, and it stably binds Zn(II). The goal of this study was to map the determinant conferring lability in Zn(II) binding by using finger pair chimeras. Whereas ZF2 contains the transactivation function, zinc regulation is dependent on the presence of ZF1. ZF3 can functionally replace ZF1, and a ZF3/2 finger pair retains limited zinc regulation. Replacement of ZF3 by ZF1 creating a ZF1/4 chimera was found to stably bind Zn(II), suggesting that the presence of a stable motif (ZF4) can impart binding stability on a labile motif (ZF1). Zn(II) binding in finger pair domains is dependent on the presence of both motifs. Mutations in one finger motif markedly attenuate Zn(II) binding to the second motif. Kinetic lability in Zn(II) binding was mapped to the alpha-helix of ZF2. A ZF1/ZFbeta2alpha4 chimera resembles ZF3/4 in Zn(II) binding stability in incubation studies with the Zn(II) chelators. The present results demonstrate that zinc regulation of AD activity of ZF2 is dependent on determinants in ZF1 as well as the alpha-helix segment of ZF2.
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PMID:Zinc metalloregulation of the zinc finger pair domain. 1682 33

Previous studies suggested that the zinc-responsive Zap1 transcriptional activator directly regulates the expression of over 80 genes in Saccharomyces cerevisiae. Many of these genes play key roles to enhance the ability of yeast cells to grow under zinc-limiting conditions. Zap1 is unusual among transcriptional activators in that it contains two activation domains, designated AD1 and AD2, which are regulated independently by zinc. These two domains are evolutionarily conserved among Zap1 orthologs suggesting that they are both important for Zap1 function. In this study, we have examined the roles of AD1 and AD2 in low zinc growth and the regulation of Zap1 target gene expression. Using alleles that are specifically disrupted for either AD1 or AD2 function, we found that these domains are not redundant, and both are important for normal growth in low zinc. AD1 plays the primary role in zinc-responsive gene regulation, whereas AD2 is required for maximal expression of only a few target promoters. AD1 alone is capable of driving full expression of most Zap1 target genes and dictates the kinetics of Zap1 gene induction in response to zinc withdrawal. Surprisingly, we found that AD1 is less active in zinc-limited cells under heat stress and AD2 plays a more important role under those conditions. These results suggest that AD2 may contribute more to Zap1 function when zinc deficiency is combined with other environmental stresses. In the course of these studies, we also found that the heat shock response is induced under conditions of severe zinc deficiency.
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PMID:Roles of two activation domains in Zap1 in the response to zinc deficiency in Saccharomyces cerevisiae. 2117 62