Last updated on 2019-09-30 by Xiang-Jun Lu <xiangjun@x3dna.org>.
The block schematics were created with DSSR and
rendered using PyMOL.
- PDB-id
- 5KL5
- Class
- transcription-DNA
- Method
- X-ray (2.29 Å)
- Summary
- Wilms tumor protein (wt1) znf2-4 q369h in complex with carboxylated DNA
List of 1 5mC-amino acid contact:
-
C.5CM3: other-contacts is-WC-paired is-in-duplex [-]:cGT/AcG
direct SNAP output · DNAproDB 2.0
- Reference
- Hashimoto, H., Zhang, X., Zheng, Y., Wilson, G.G., Cheng, X.: (2016) "Denys-Drash syndrome associated WT1 glutamine 369 mutants have altered sequence-preferences and altered responses to epigenetic modifications." Nucleic Acids Res., 44, 10165-10176.
- Abstract
- Mutations in human zinc-finger transcription factor WT1 result in abnormal development of the kidneys and genitalia and an array of pediatric problems including nephropathy, blastoma, gonadal dysgenesis and genital discordance. Several overlapping phenotypes are associated with WT1 mutations, including Wilms tumors, Denys-Drash syndrome (DDS), Frasier syndrome (FS) and WAGR syndrome (Wilms tumor, aniridia, genitourinary malformations, and mental retardation). These conditions vary in severity from individual to individual; they can be fatal in early childhood, or relatively benign into adulthood. DDS mutations cluster predominantly in zinc fingers (ZF) 2 and 3 at the C-terminus of WT1, which together with ZF4 determine the sequence-specificity of DNA binding. We examined three DDS associated mutations in ZF2 of human WT1 where the normal glutamine at position 369 is replaced by arginine (Q369R), lysine (Q369K) or histidine (Q369H). These mutations alter the sequence-specificity of ZF2, we find, changing its affinity for certain bases and certain epigenetic forms of cytosine. X-ray crystallography of the DNA binding domains of normal WT1, Q369R and Q369H in complex with preferred sequences revealed the molecular interactions responsible for these affinity changes. DDS is inherited in an autosomal dominant fashion, implying a gain of function by mutant WT1 proteins. This gain, we speculate, might derive from the ability of the mutant proteins to sequester WT1 into unproductive oligomers, or to erroneously bind to variant target sequences.
- The 5-methylcytosine group (PDB ligand '5CM') is shown in space-filling model,
with the methyl-carbon atom in black.
- Watson-Crick base pairs are represented as long rectangular blocks with the
minor-groove edge in black. Color code: A-T red, C-G yellow, G-C green, T-A blue.
- Protein is shown as cartoon in purple. DNA backbones are shown ribbon, colored code
by chain identifier.
- The block schematics were created with 3DNA-DSSR,
and images were rendered using PyMOL.
- Download the PyMOL session file corresponding to the top-left
image in the following panel.
- The contacts include paired nucleotides (mostly a G in G-C pairing), and
amino-acids within a 4.5-A distance cutoff to the base atoms of 5mC.
- The structure is oriented in the 'standard' base reference frame of 5mC, allowing for easy comparison
and direct superimposition between entries.
- The black sphere (•) denotes the 5-methyl carbon atom in 5mC.
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No. 1 C.5CM3: download PDB file
for the 5mC entry
other-contacts is-WC-paired is-in-duplex [-]:cGT/AcG
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