7DTA

Solution structure of the C-clamp domain from human HDBP1 in complex with DNA

7DTA の概要

• エントリーDOI: 10.2210/pdb7dta/pdb
• NMR情報: BMRB: 36404
• 分子名称: SLC2A4 regulator, DNA (5'-D(*TP*AP*TP*GP*CP*CP*GP*GP*GP*AP*C)-3'), DNA (5'-D(*GP*TP*CP*CP*CP*GP*GP*CP*AP*TP*A)-3'), ... (4 entities in total)
• 機能のキーワード: c-clamp, zinc finger, unmethylated cpg binding, dna binding protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 10806.62

構造登録者

Duan, B.,Xia, B. (登録日: 2021-01-04, 公開日: 2021-07-21, 最終更新日: 2024-05-01)

主引用文献

Duan, B.,Fu, D.,Zhang, C.,Ding, P.,Dong, X.,Xia, B.
Selective Nonmethylated CpG DNA Recognition Mechanism of Cysteine Clamp Domains.
J.Am.Chem.Soc., 143:7688-7697, 2021

PubMed Abstract: Methylation of DNA at CpG sites is a major mark for epigenetic regulation, but how transcription factors are influenced by CpG methylation is not well understood. Here, we report the molecular mechanisms of how the TCF (T-cell factor) and GEF (glucose transporter 4 enhancer factor) families of proteins selectively target unmethylated DNA sequences with a C-clamp type zinc finger domain. The structure of the C-clamp domain from human GEF family protein HDBP1 (C-clamp) in complex with DNA was determined using NMR spectroscopy, which adopts a unique zinc finger fold and selectively binds RCCGG (R = A/G) DNA sequences with an "Arg···Trp-Lys-Lys" DNA recognition motif inserted in the major groove. The CpG base pairs are central to the binding due to multiple hydrogen bonds formed with the backbone carbonyl groups of Trp378 and Lys379, as well as the side chain ε-amino groups of Lys379 and Lys380 from C-clamp. Consequently, methylation of the CpG dinucleotide almost abolishes the binding. Homology modeling reveals that the C-clamp domain from human TCF1E (C-clamp) binds DNA through essentially the same mechanism, with a similar "Arg···Arg-Lys-Lys" DNA recognition motif. The substitution of tryptophan by arginine makes C-clamp prefer RCCGC DNA sequences. The two signature DNA recognition motifs are invariant in the GEF and TCF families of proteins, respectively, from fly to human. The recognition of the CpG dinucleotide through two consecutive backbone carbonyl groups is the same as that of the CXXC type unmethylated CpG DNA binding domains, suggesting a common mechanism shared by unmethylated CpG binding proteins.

PubMed: 33983734
DOI: 10.1021/jacs.1c00599

実験手法

SOLUTION NMR