8ALQ

The Solution Structure of the Triple Mutant Methyl-CpG-Binding Domain from MeCP2 that Binds to Asymmetrically Modified DNA

8ALQ の概要

• エントリーDOI: 10.2210/pdb8alq/pdb
• NMR情報: BMRB: 34745
• 分子名称: Methyl-CpG-binding protein 2 (1 entity in total)
• 機能のキーワード: hmc-mc complex, gene regulation, methyl-cpg-binding domain (mbd) of mecp2, dna binding protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 11905.29

構造登録者

Singh, H. (登録日: 2022-08-01, 公開日: 2023-02-22, 最終更新日: 2024-06-19)

主引用文献

Singh, H.,Das, C.K.,Buchmuller, B.C.,Schafer, L.V.,Summerer, D.,Linser, R.
Epigenetic CpG duplex marks probed by an evolved DNA reader via a well-tempered conformational plasticity.
Nucleic Acids Res., 51:6495-6506, 2023

PubMed Abstract: 5-methylcytosine (mC) and its TET-oxidized derivatives exist in CpG dyads of mammalian DNA and regulate cell fate, but how their individual combinations in the two strands of a CpG act as distinct regulatory signals is poorly understood. Readers that selectively recognize such novel 'CpG duplex marks' could be versatile tools for studying their biological functions, but their design represents an unprecedented selectivity challenge. By mutational studies, NMR relaxation, and MD simulations, we here show that the selectivity of the first designer reader for an oxidized CpG duplex mark hinges on precisely tempered conformational plasticity of the scaffold adopted during directed evolution. Our observations reveal the critical aspect of defined motional features in this novel reader for affinity and specificity in the DNA/protein interaction, providing unexpected prospects for further design progress in this novel area of DNA recognition.

PubMed: 36919612
DOI: 10.1093/nar/gkad134

実験手法

SOLUTION NMR