DNAproDB: an interactive tool for structural analysis of DNA–protein complexes

Sagendorf, Jared M.; Berman, Helen M.; Rohs, Remo

doi:10.1093/nar/gkx272

Cited by 67 publications

(59 citation statements)

References 50 publications

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“…To examine the structural basis of the differences in DNA binding between Zta and C189 mutants, we examined nucleotide-residue contact maps [21] for Zta(C189S) (PDB: 5szx [7]) (Fig S9A) binding the canonical meZRE2 motif ( TGAGM 2 GA , complement: TM −3’ GCTCA ) and a structure where serine is changed to cysteine (Fig S9B). As summarized in the introduction, the serine in Zta(C189S) of each Zta monomer interacts via hydrogen bonds (bold red lines, Fig S9A) with the phosphate backbone upstream of the thymines at each end of the meZRE2 ( T −4 and T −4’ ), as well as additional van der Waals interactions with T −4 and the methylated cytosine of the opposite strand of meZRE2 ( M −3’ ) (bold black lines, Fig S9A and [7]).…”

Section: Resultsmentioning

confidence: 99%

Replacing C189 in the bZIP domain of Zta with S, T, V, or A changes DNA binding specificity to four types of double-stranded DNA

Ray

Tillo

Assad

et al. 2018

Biochemical and Biophysical Research Communications

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Zta is a bZIP transcription factor (TF) in the Epstein-Barr virus that binds unmethylated and methylated DNA sequences. Substitution of cysteine 189 of Zta to serine (Zta(C189S)) results in a virus that is unable to execute the lytic cycle, which was attributed to a change in binding to methylated DNA sequences. To learn more about the role of this position in defining sequence-specific DNA binding, we mutated cysteine 189 to four other amino acids, producing Zta(C189S), Zta(C189T), Zta(C189A), and Zta(C189V) mutants. Zta and mutants were used in protein binding microarray (PBM) experiments to evaluate sequence-specific DNA binding to four types of double-stranded DNA (dsDNA): 1) with cytosine in both strands (DNA(C|C)), 2) with 5-methylcytosine (5mC) in one strand and cytosine in the second strand (DNA(5mC|C)), 3) with 5-hydroxymethylcytosine (5hmC) in one strand and cytosine in the second strand (DNA(5hmC|C)), and 4) with both cytosines in all CG dinucleotides containing 5mC (DNA(5mCG)). Zta(C189S) and Zta(C189T) bound the TRE (AP-1) motif (TGA/TCA) more strongly than wild-type Zta, while binding to other sequences, including the C/EBP half site GCAA was reduced. Binding of Zta(C189S) and Zta(C189T) to DNA containing modified cytosines (DNA(5mC|C), DNA(5hmC|C), and DNA(5mCG)) was reduced compared to Zta. Zta(C189A) and Zta(C189V) had higher non-specific binding to all four types of DNA. Our data suggests that position C189 in Zta impacts sequence-specific binding to DNA containing modified and unmodified cytosine.

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Section: Resultsmentioning

confidence: 99%

Replacing C189 in the bZIP domain of Zta with S, T, V, or A changes DNA binding specificity to four types of double-stranded DNA

Ray

Tillo

Assad

et al. 2018

Biochemical and Biophysical Research Communications

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“…In order to study the structural variations induced upon binding of different FOX proteins to the same DNA sequence, we compared the DNA conformation of our FOXA2 complex to that of the previously published FOXO1 31 , both bound to DNA sequence DBE2 (Figure 6). The proteins shared similar overall structures, with slight differences in the wing 1 region and the N-terminal tail (Figure 6A).…”

Section: Resultsmentioning

confidence: 99%

“…Figures were generated by PyMol 30 . DNAproDB was used to generate schematic diagrams of protein-nucleic acid interactions 31 .…”

Section: Methodsmentioning

confidence: 99%

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Structure of the Forkhead Domain of FOXA2 Bound to a Complete DNA Consensus Site

Machado

Guo

et al. 2017

Biochemistry

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FOXA2, a member of the forkhead family of transcription factors, plays essential roles in liver development and bile acid homeostasis. In this study, we report a 2.8 Å co-crystal structure of the FOXA2 DNA-binding domain (FOXA2-DBD) bound to a DNA duplex containing a forkhead consensus binding site (GTAAACA). FOXA2-DBD adopts the canonical winged-helix fold, with helix H3 and wing 1 regions mainly mediating the DNA recognition. Although the wing 2 region was not defined in the structure, isothermal titration calorimetry (ITC) assays suggested that this region was required for optimal DNA binding. Structure comparison with the FOXA3-DBD bound to DNA revealed more major groove contacts and less minor groove contacts in the FOXA2 structure compared to the FOXA3 structure. Structure comparison with the FOXO1-DBD bound to DNA showed that different forkhead proteins could induce different DNA conformations upon binding to identical DNA sequences. Our findings provide the structural basis for FOXA2 protein binding to a consensus forkhead site and elucidate how members of the forkhead protein family bind different DNA sites.

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“…One TRE half site ( ) is colored in green. (B) Nucleotide-residue interaction map 30 generated using PDB structure 2c9l 29 of Zta binding the TRE sequence. Amino acids from each monomer and specific nucleotides are colored as in A. Interactions between the thymines in the TRE half site (highlighted) with the sequential Alanine (Ala185) and Serine (Ser186) interactions are indicated with bold lines.…”

Section: Figurementioning

confidence: 99%

The Epstein-Barr Virus B-ZIP Protein Zta Recognizes Specific DNA Sequences Containing 5-Methylcytosine and 5-Hydroxymethylcytosine

Tillo¹,

Ray²,

Khund-Sayeed³

et al. 2017

Biochemistry

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The Epstein-Barr virus (EBV) B-ZIP transcription factor (TF) Zta binds to many DNA sequences containing methylated CG dinucleotides. Using protein binding microarrays (PBMs), we analyzed the sequence specific DNA binding of Zta to four kinds of double-stranded DNA (dsDNA): 1) DNA containing cytosine in both strands, 2) DNA with 5-methylcytosine (5mC) in one strand and cytosine in the second strand, 3) DNA with 5-hydroxymethylcytosine (5hmC) in one strand and cytosine in the second strand, and 4) DNA where both cytosines in all CG dinucleotides contain 5mC. We compared these data to PBM data for three additional B-ZIP proteins (CREB1 and CEBPB homodimers, and cJun|cFos heterodimers). With cytosine, Zta binds the TRE motif as previously reported. With CG dinucleotides containing 5mC on both strands, many TRE motif variants containing a methylated CG dinucleotide at two positions in the motif, such as and (where =5mC) were preferentially bound. 5mC inhibits Zta binding to both TRE motif half sites and . Like the CREB1 homodimer, the Zta homodimer and the cJun|cFos heterodimer bind the C/EBP half site tetranucleotide stronger when it contains 5mC. Zta also binds dsDNA sequences containing 5hmC in one strand, although the effect is less dramatic than observed for 5mC. Our results identify new DNA sequences that are well-bound by the viral B-ZIP protein Zta only when they contain 5mC or 5hmC, uncovering the potential for discovery of new viral and host regulatory programs controlled by EBV.

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DNAproDB: an interactive tool for structural analysis of DNA–protein complexes

Cited by 67 publications

References 50 publications

Replacing C189 in the bZIP domain of Zta with S, T, V, or A changes DNA binding specificity to four types of double-stranded DNA

Replacing C189 in the bZIP domain of Zta with S, T, V, or A changes DNA binding specificity to four types of double-stranded DNA

Structure of the Forkhead Domain of FOXA2 Bound to a Complete DNA Consensus Site

The Epstein-Barr Virus B-ZIP Protein Zta Recognizes Specific DNA Sequences Containing 5-Methylcytosine and 5-Hydroxymethylcytosine

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