Solution structure of the matrix attachment region-binding domain of chicken MeCP2

Heitmann, Björn and Maurer, Till and Weitzel, Joachim M. and Strawtling, Wolf H. and Kalbitzer, Hans Robert and Brunner, Eike (2003) Solution structure of the matrix attachment region-binding domain of chicken MeCP2. EUROPEAN JOURNAL OF BIOCHEMISTRY, 270 (15). pp. 3263-3270. ISSN 0014-2956

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Abstract

Methyl-CpG-binding protein 2 (MeCP2) is a multifunctional protein involved in chromatin organization and silencing of methylated DNA. MAR-BD, a 125-amino-acid residue domain of chicken MeCP2 (cMeCP2, originally named ARBP), is the minimal protein fragment required to recognize MAR elements and mouse satellite DNA. Here we report the solution structure of MAR-BD as determined by multidimensional heteronuclear NMR spectroscopy. The global fold of this domain is very similar to that of rat MeCP2 MBD and MBD1 MBD (the methyl-CpG-binding domains of rat MeCP2 and methyl-CpG-binding domain protein 1, respectively), exhibiting a three-stranded antiparallel beta-sheet and an alpha-helix alpha(1) . We show that the C-terminal portion of MAR-BD also contains an amphipathic helical coil, alpha(2) /alpha(3) . The hydrophilic residues of this coil form a surface opposite the DNA interface, available for interactions with other domains of MeCP2 or other proteins. Spectroscopic studies of the complex formed by MAR-BD and a 15-bp fragment of a high-affinity binding site from mouse satellite DNA indicates that the coil is also involved in protein.DNA interactions. These studies provide a basis for discussion of the consequences of six missense mutations within the helical coil found in Rett syndrome cases.

Item Type: Article
Uncontrolled Keywords: PROTEIN SECONDARY STRUCTURE; METHYLATED DNA; RETT-SYNDROME; TRANSCRIPTIONAL REPRESSION; CHROMOSOMAL PROTEIN; CHEMICAL-SHIFT; NMR-SPECTRA; SEQUENCE; PROGRAM; C-13; chicken methyl-CpG-binding protein 2 (cMeCP2); MAR-binding protein (ARBP); NMR spectroscopy; protein center dot DNA interaction
Subjects: 500 Science > 540 Chemistry & allied sciences
Divisions: Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie > Alumni or Retired > Prof. Dr. Eike Brunner
Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie > Prof. Dr. Dr. Hans Robert Kalbitzer
Depositing User: Dr. Gernot Deinzer
Date Deposited: 04 Aug 2021 12:48
Last Modified: 04 Aug 2021 12:48
URI: https://pred.uni-regensburg.de/id/eprint/38762

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