4R2Q

Wilms Tumor Protein (WT1) zinc fingers in complex with formylated DNA

Summary for 4R2Q

• Entry DOI: 10.2210/pdb4r2q/pdb
• Related: 4R2A 4R2C 4R2D 4R2E 4R2P 4R2R 4R2S
• Descriptor: Wilms tumor protein, isoform 4/CRA_a, DNA (5'-D(*AP*GP*CP*GP*TP*GP*GP*GP*(5FC)P*GP*T)-3'), DNA (5'-D(*TP*AP*(5FC)P*GP*CP*CP*CP*AP*CP*GP*C)-3'), ... (6 entities in total)
• Functional Keywords: zinc finger, transcription, dna binding protein-dna complex, dna binding protein/dna
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus. Isoform 1: Nucleus speckle. Isoform 4: Nucleus, nucleoplasm: P19544
• Total number of polymer chains: 3
• Total formula weight: 18306.58

Authors

Hashimoto, H.,Olanrewaju, Y.O.,Zheng, Y.,Wilson, G.G.,Zhang, X.,Cheng, X. (deposition date: 2014-08-12, release date: 2014-10-08, Last modification date: 2023-09-20)

Primary citation

Hashimoto, H.,Olanrewaju, Y.O.,Zheng, Y.,Wilson, G.G.,Zhang, X.,Cheng, X.
Wilms tumor protein recognizes 5-carboxylcytosine within a specific DNA sequence.
Genes Dev., 28:2304-2313, 2014

PubMed Abstract: In mammalian DNA, cytosine occurs in several chemical forms, including unmodified cytosine (C), 5-methylcytosine (5 mC), 5-hydroxymethylcytosine (5 hmC), 5-formylcytosine (5 fC), and 5-carboxylcytosine (5 caC). 5 mC is a major epigenetic signal that acts to regulate gene expression. 5 hmC, 5 fC, and 5 caC are oxidized derivatives that might also act as distinct epigenetic signals. We investigated the response of the zinc finger DNA-binding domains of transcription factors early growth response protein 1 (Egr1) and Wilms tumor protein 1 (WT1) to different forms of modified cytosine within their recognition sequence, 5'-GCG(T/G)GGGCG-3'. Both displayed high affinity for the sequence when C or 5 mC was present and much reduced affinity when 5 hmC or 5 fC was present, indicating that they differentiate primarily oxidized C from unoxidized C, rather than methylated C from unmethylated C. 5 caC affected the two proteins differently, abolishing binding by Egr1 but not by WT1. We ascribe this difference to electrostatic interactions in the binding sites. In Egr1, a negatively charged glutamate conflicts with the negatively charged carboxylate of 5 caC, whereas the corresponding glutamine of WT1 interacts with this group favorably. Our analyses shows that zinc finger proteins (and their splice variants) can respond in modulated ways to alternative modifications within their binding sequence.

PubMed: 25258363
DOI: 10.1101/gad.250746.114

Experimental method

X-RAY DIFFRACTION (1.54 Å)