Zinc Binding Properties of the DNA Binding Domain of the 1,25-Dihydroxyvitamin D3Receptor†

Biochemistry ◽  
1997 ◽  
Vol 36 (34) ◽  
pp. 10482-10491 ◽  
Author(s):  
Theodore A. Craig ◽  
Timothy D. Veenstra ◽  
Stephen Naylor ◽  
Andy J. Tomlinson ◽  
Kenneth L. Johnson ◽  
...  
Keyword(s):  
Dna Binding ◽  
Binding Domain ◽  
Zinc Binding ◽  
Dna Binding Domain ◽  
Binding Properties

scholarly journals Role of cysteine residues in regulation of p53 function.

1995 ◽  
Vol 15 (7) ◽  
pp. 3892-3903 ◽  
Author(s):  
R Rainwater ◽  
D Parks ◽  
M E Anderson ◽  
P Tegtmeyer ◽  
K Mann
Keyword(s):  
Dna Binding ◽  
Transcriptional Activation ◽  
Redox Regulation ◽  
Binding Domain ◽  
Zinc Binding ◽  
Cysteine Residues ◽  
Dna Binding Domain ◽  
Site Specific ◽  
Functional Consequences

Previous studies of p53 have implicated cysteine residues in site-specific DNA binding via zinc coordination and redox regulation (P. Hainaut and J. Milner, Cancer Res. 53:4469-4473, 1993; T. R. Hupp, D. W. Meek, C. A. Midgley, and D. P. Lane, Nucleic Acids Res. 21:3167-3174, 1993). We show here that zinc binding and redox regulation are, at least in part, distinct determinants of the binding of p53 to DNA. Moreover, by substituting serine for each cysteine in murine p53, we have investigated the roles of individual cysteines in the regulation of p53 function. Substitution of serine for cysteine at position 40, 179, 274, 293, or 308 had little or no effect on p53 function. In contrast, replacement of cysteine at position 173, 235, or 239 markedly reduced in vitro DNA binding, completely blocked transcriptional activation, and led to a striking enhancement rather than a suppression of transformation by p53. These three cysteines have been implicated in zinc binding by X-ray diffraction studies (Y. Cho, S. Gorina, P.D. Jeffrey, and N.P. Pavletich, Science 265:346-355, 1994); our studies demonstrate the functional consequences of the inability of the central DNA-binding domain of p53 to studies demonstrate the functional consequences of the inability of the central DNA-binding domain of p53 to bind zinc. Lastly, substitutions for cysteines at position 121, 132, 138, or 272 partially blocked both transactivation and the suppression of transformation by p53. These four cysteines are located in the loop-sheet-helix region of the site-specific DNA-binding domain of p53. Like the cysteines in the zinc-binding region, therefore, these cysteines may cooperate to modulate the structure of the DNA-binding domain. Our findings argue that p53 is subject to more than one level of conformational modulation through oxidation-reduction of cysteines at or near the p53-DNA interface.

Localization of the Zinc-Binding Sites in the DNA-Binding Domain of the Bovine Poly(ADP-Ribose) Polymerase

1989 ◽  
pp. 89-93 ◽  
Author(s):  
Alice Mazen ◽  
Daniel Lamarre ◽  
Guy Poirier ◽  
Gérard Gradwohl ◽  
Gilbert de Murcia
Keyword(s):  
Dna Binding ◽  
Binding Sites ◽  
Binding Domain ◽  
Zinc Binding ◽  
Dna Binding Domain

Mutational analysis of the GAL4-encoded transcriptional activator protein of Saccharomyces cerevisiae.

Genetics ◽  
1988 ◽  
Vol 120 (1) ◽  
pp. 63-74
Author(s):  
M Johnston ◽  
J Dover
Keyword(s):  
Amino Acid ◽  
Dna Binding ◽  
Zinc Finger ◽  
Transcription Activation ◽  
Binding Domain ◽  
Zinc Binding ◽  
Zinc Ions ◽  
Dna Binding Domain ◽  
Activation Domain ◽  
Transcription Activation Domain

Abstract The GAL4 protein of Saccharomyces cerevisiae binds to DNA upstream of each of six genes and stimulates their transcription. To locate regions of the protein responsible for these processes, we identified and characterized 88 gal4 mutations selected in vivo to reduce the ability to GAL4 protein to activate transcription. These mutations alter two regions of GAL4 protein: the DNA binding domain, and the transcription activation domain. Some mutations in the DNA binding domain that abolish the ability of GAL4 protein to bind to DNA in vitro change amino acid residues proposed to form a zinc finger, confirming that this structure is indeed involved in DNA binding. Four different amino acid changes in the zinc finger appear to reduce (but not abolish) the affinity of GAL4 protein for zinc ions, thereby identifying some of the amino acids involved in forming the zinc-binding structure. Several other mutations that abolish the DNA binding activity of the protein alter the 20 amino acids adjacent to the zinc finger, suggesting that these residues are part of the DNA binding domain. Two amino acid changes in the region adjacent to the zinc finger also appear to affect the ability of GAL4 protein to bind zinc ions, suggesting that this region of the protein can influence the structure of the zinc binding domain. The transcription activation domain of GAL4 protein is remarkably resistant to single amino acid changes: only 4 of the 42 mutations that alter this region of the protein are of the missense type. This observation is consistent with other lines of evidence that GAL4 protein possesses multiple transcription activation domains with unusual sequence flexibility.

NMR studies of the R2 repeat and related peptide fragments of the DNA binding domain of c-Myb. New light on the structure and folding of R2.

1999 ◽  
Vol 96 (9/10) ◽  
pp. 1580-1584 ◽  
Author(s):  
I. Ségalas ◽  
S. Desjardins ◽  
H. Oulyadi ◽  
Y. Prigent ◽  
S. Tribouillard ◽  
...  
Keyword(s):  
Dna Binding ◽  
Binding Domain ◽  
Dna Binding Domain ◽  
Peptide Fragments ◽  
Nmr Studies ◽  
Related Peptide

scholarly journals Primary structure of a glycosylated DNA-binding domain in human plasma fibronectin.

1985 ◽  
Vol 260 (4) ◽  
pp. 2301-2306
Author(s):  
H Pande ◽  
J Calaycay ◽  
D Hawke ◽  
C M Ben-Avram ◽  
J E Shively
Keyword(s):  
Dna Binding ◽  
Human Plasma ◽  
Primary Structure ◽  
Binding Domain ◽  
Dna Binding Domain ◽  
Plasma Fibronectin
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