6ML3

ZBTB24 Zinc Fingers 4-8 with 19+1mer DNA Oligonucleotide (Sequence 2)

6ML3 の概要

• エントリーDOI: 10.2210/pdb6ml3/pdb
• 分子名称: Zinc finger and BTB domain-containing protein 24, DNA (5'-D(*AP*CP*GP*CP*AP*GP*GP*TP*CP*CP*TP*GP*GP*AP*AP*GP*CP*TP*AP*A)-3'), DNA (5'-D(*TP*TP*TP*AP*GP*CP*TP*TP*CP*CP*AP*GP*GP*AP*CP*CP*TP*GP*CP*G)-3'), ... (6 entities in total)
• 機能のキーワード: protein-dna complex, transcription, transcription-dna complex, transcription/dna
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 29932.09

構造登録者

Horton, J.R.,Cheng, X.,Ren, R. (登録日: 2018-09-26, 公開日: 2019-07-03, 最終更新日: 2023-10-11)

主引用文献

Ren, R.,Hardikar, S.,Horton, J.R.,Lu, Y.,Zeng, Y.,Singh, A.K.,Lin, K.,Coletta, L.D.,Shen, J.,Lin Kong, C.S.,Hashimoto, H.,Zhang, X.,Chen, T.,Cheng, X.
Structural basis of specific DNA binding by the transcription factor ZBTB24.
Nucleic Acids Res., 47:8388-8398, 2019

PubMed Abstract: ZBTB24, encoding a protein of the ZBTB family of transcriptional regulators, is one of four known genes-the other three being DNMT3B, CDCA7 and HELLS-that are mutated in immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome, a genetic disorder characterized by DNA hypomethylation and antibody deficiency. The molecular mechanisms by which ZBTB24 regulates gene expression and the biological functions of ZBTB24 are poorly understood. Here, we identified a 12-bp consensus sequence [CT(G/T)CCAGGACCT] occupied by ZBTB24 in the mouse genome. The sequence is present at multiple loci, including the Cdca7 promoter region, and ZBTB24 binding is mostly associated with gene activation. Crystallography and DNA-binding data revealed that the last four of the eight zinc fingers (ZFs) (i.e. ZF5-8) in ZBTB24 confer specificity of DNA binding. Two ICF missense mutations have been identified in the ZBTB24 ZF domain, which alter zinc-binding cysteine residues. We demonstrated that the corresponding C382Y and C407G mutations in mouse ZBTB24 abolish specific DNA binding and fail to induce Cdca7 expression. Our analyses indicate and suggest a structural basis for the sequence specific recognition by a transcription factor centrally important for the pathogenesis of ICF syndrome.

PubMed: 31226215
DOI: 10.1093/nar/gkz557

実験手法

X-RAY DIFFRACTION (1.683 Å)