6E93

Crystal Structure of ZBTB38 C-terminal Zinc Fingers 6-9 in complex with methylated DNA

6E93 の概要

• エントリーDOI: 10.2210/pdb6e93/pdb
• 分子名称: Zinc finger and BTB domain-containing protein 38, DNA (5'-D(*GP*TP*CP*TP*GP*(DCM)P*GP*CP*(DCM)P*GP*AP*TP*GP*AP*GP*TP*GP*C)-3'), DNA (5'-D(*GP*CP*AP*CP*TP*CP*AP*TP*(DCM)P*GP*GP*(DCM)P*GP*CP*AP*GP*AP*C)-3'), ... (5 entities in total)
• 機能のキーワード: zbtb38 methylated dna zinc finger, dna binding protein, dna binding protein-dna complex, dna binding protein/dna
• 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: 25588.36

構造登録者

Hudson, N.O.,Whitby, F.G.,Buck-Koehntop, B.A. (登録日: 2018-07-31, 公開日: 2018-11-07, 最終更新日: 2024-03-13)

主引用文献

Hudson, N.O.,Whitby, F.G.,Buck-Koehntop, B.A.
Structural insights into methylated DNA recognition by the C-terminal zinc fingers of the DNA reader protein ZBTB38.
J. Biol. Chem., 293:19835-19843, 2018

PubMed Abstract: Methyl-CpG-binding proteins (MBPs) are selective readers of DNA methylation that play an essential role in mediating cellular transcription processes in both normal and diseased cells. This physiological function of MBPs has generated significant interest in understanding the mechanisms by which these proteins read and interpret DNA methylation signals. Zinc finger and BTB domain-containing 38 (ZBTB38) represents one member of the zinc finger (ZF) family of MBPs. We recently demonstrated that the C-terminal ZFs of ZBTB38 exhibit methyl-selective DNA binding within the ((A/G)TmCG(G/A)(mC/T)(G/A)) context both and within cells. Here we report the crystal structure of the first four C-terminal ZBTB38 ZFs (ZFs 6-9) in complex with the previously identified methylated consensus sequence at 1.75 Å resolution. From the structure, methyl-selective binding is preferentially localized at the 5' mCpG site of the bound DNA, which is facilitated through a series of base-specific interactions from residues within the α-helices of ZF7 and ZF8. ZF6 and ZF9 primarily stabilize ZF7 and ZF8 to facilitate the core base-specific interactions. Further structural and biochemical analyses, including solution NMR spectroscopy and electrophoretic mobility gel shift assays, revealed that the C-terminal ZFs of ZBTB38 utilize an alternative mode of mCpG recognition from the ZF MBPs structurally evaluated to date. Combined, these findings provide insight into the mechanism by which this ZF domain of ZBTB38 selectively recognizes methylated CpG sites and expands our understanding of how ZF-containing proteins can interpret this essential epigenetic mark.

PubMed: 30355731
DOI: 10.1074/jbc.RA118.005147

実験手法

X-RAY DIFFRACTION (1.747 Å)