2KY8

Solution structure and dynamic analysis of chicken MBD2 methyl binding domain bound to a target methylated DNA sequence

2KY8 の概要

• エントリーDOI: 10.2210/pdb2ky8/pdb
• 関連するPDBエントリー: 1IG4 3C2I
• NMR情報: BMRB: 16936
• 分子名称: Methyl-CpG-binding domain protein 2, DNA (5'-D(*GP*GP*AP*AP*TP*(5CM)P*GP*GP*CP*(TED)P*C)-3'), DNA (5'-D(*GP*AP*GP*CP*(5CM)P*GP*AP*TP*(TED)P*CP*C)-3'), ... (4 entities in total)
• 機能のキーワード: dna binding domain, transcription-dna complex, transcription/dna
• 由来する生物種: Gallus gallus (bantam,chickens)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 15596.19

構造登録者

Williams Jr., D.C.,Scarsdale Jr., J.N. (登録日: 2010-05-18, 公開日: 2011-05-18, 最終更新日: 2024-05-01)

主引用文献

Scarsdale, J.N.,Webb, H.D.,Ginder, G.D.,Williams, D.C.
Solution structure and dynamic analysis of chicken MBD2 methyl binding domain bound to a target-methylated DNA sequence.
Nucleic Acids Res., 39:6741-6752, 2011

PubMed Abstract: The epigenetic code of DNA methylation is interpreted chiefly by methyl cytosine binding domain (MBD) proteins which in turn recruit multiprotein co-repressor complexes. We previously isolated one such complex, MBD2-NuRD, from primary erythroid cells and have shown it contributes to embryonic/fetal β-type globin gene silencing during development. This complex has been implicated in silencing tumor suppressor genes in a variety of human tumor cell types. Here we present structural details of chicken MBD2 bound to a methylated DNA sequence from the ρ-globin promoter to which it binds in vivo and mediates developmental transcriptional silencing in normal erythroid cells. While previous studies have failed to show sequence specificity for MBD2 outside of the symmetric mCpG, we find that this domain binds in a single orientation on the ρ-globin target DNA sequence. Further, we show that the orientation and affinity depends on guanine immediately following the mCpG dinucleotide. Dynamic analyses show that DNA binding stabilizes the central β-sheet, while the N- and C-terminal regions of the protein maintain mobility. Taken together, these data lead to a model in which DNA binding stabilizes the MBD2 structure and that binding orientation and affinity is influenced by the DNA sequence surrounding the central mCpG.

PubMed: 21531701
DOI: 10.1093/nar/gkr262

実験手法

SOLUTION NMR