1QK9

The solution structure of the domain from MeCP2 that binds to methylated DNA

1QK9 の概要

• エントリーDOI: 10.2210/pdb1qk9/pdb
• 分子名称: METHYL-CPG-BINDING PROTEIN 2 (1 entity in total)
• 機能のキーワード: methyl-cpg-binding protein, solution structure, methylated dna, methyl cytosine, mbd
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Nucleus : P51608
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 10261.53

構造登録者

Wakefield, R.I.D.,Smith, B.O.,Nan, X.,Free, A.,Soteriou, A.,Uhrin, D.,Bird, A.P.,Barlow, P.N. (登録日: 1999-07-12, 公開日: 1999-10-08, 最終更新日: 2024-05-15)

主引用文献

Wakefield, R.I.D.,Smith, B.O.,Nan, X.,Free, A.,Soteriou, A.,Uhrin, D.,Bird, A.P.,Barlow, P.N.
The Solution Structure of the Domain from Mecp2 that Binds to Methylated DNA
J.Mol.Biol., 291:1055-, 1999

PubMed Abstract: MeCP2 is an abundant mammalian protein that binds methylated CpG (mCpG) sequences within double-stranded DNA, represses transcription by recruiting histone deacetylases, and is essential for embryonic development. It is one of a family of proteins which mediate the biological consequences of DNA methylation. These proteins each possess a sequence motif of about 70 residues which, in MeCP2, form a domain necessary and sufficient for binding to mCpG. The solution structure of the mCpG-binding domain (MBD) from MeCP2 has been solved and the DNA-binding surface of the domain mapped using NMR spectroscopy. Residues 95-162 of MeCP2 adopt a novel fold forming a wedge-shaped structure. An N-terminal four-stranded antiparallel beta-sheet forms one face of the wedge, while the other face is formed mainly by a C-terminal helical region. The thin end of the wedge is extended by a long loop between beta-strands B and C containing many basic residues. The B-C loop together with residues in strands B, C and D, and at the N terminus of the alpha-helix, appears to form an interface with methylated DNA. Unstructured residues at the NH2 terminus of the domain are also involved in formation of the complex. The presence of numerous arginine and lysine side-chains on the DNA-binding surface of MBD is consistent with the requirement for the mCpG site to be flanked by non-specific sequences of base-pairs. The absence of symmetry in the domain implies that recognition does not exploit the symmetry of the binding site. A conserved hydrophobic pocket containing the side-chains of Tyr123 and Ile125 on the positively charged beta-sheet face is a candidate for the region of contact with the methyl-groups of the modified cytosine residues.

PubMed: 10518942
DOI: 10.1006/JMBI.1999.3023

実験手法

SOLUTION NMR