Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Zap1 transcriptional activator from Saccharomyces cerevisiae induces expression of a series of genes containing an 11 base pair conserved promoter element (ZRE) under conditions of zinc deficiency. This work shows that Zap1 uses four of its seven zinc finger domains to contact the ZRE and that two of these dominate the interaction by contacting the essential ACC-GGT ends. Two Zn finger domains (ZF1 and ZF2) do not contact DNA, and a third ZF3 may be more important for interfinger protein-protein interactions. Zn finger domains important for ZRE contact were identified from triple mutations in Zap1, changing three residues in the alpha helix in each finger known to be important for DNA contacts in Zn finger proteins. Replacement of -1, 3, and 6 helix residues in ZF4 and ZF7 reduced the affinity of Zap1 for the wild-type ZRE. In contrast, triple mutations within the intervening ZF5 and ZF6 domains had minimal effect. The data argue that fingers 4 and 7 contact the ACC-GGT ends while fingers 5 and 6 contact the 5 bp central ZRE sequence. This conclusion is corroborated by decreased Zap1 affinity for a ZRE DNA duplex containing mutations of the AC-GT ends of the ZRE, whereas transversion mutations within the central 5 bp of the ZRE had minimal effect on Zap1 binding affinity.
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PMID:Two of the five zinc fingers in the Zap1 transcription factor DNA binding domain dominate site-specific DNA binding. 1254 26

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