tailieunhanh - Báo cáo khoa học: Solution structure of the matrix attachment region-binding domain of chicken MeCP2

Methyl-CpG-binding protein 2 (MeCP2) is a multifunc-tional protein involved in chromatin organization and silencing of methylated DNA. MAR-BD, a 125-amino-acid residue domain of chicken MeCP2 (cMeCP2, origin-ally 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. | Eur. J. Biochem. 270 3263-3270 2003 FEBS 2003 doi Solution structure of the matrix attachment region-binding domain of chicken MeCP2 Bjorn Heitmann1 Till Maurer1 Joachim M. Weitzel2 3 Wolf H. Stratling2 Hans Robert Kalbitzer1 and Eike Brunner1 1Institut fur Biophysik und physikalische Biochemie Universitdt Regensburg Germany 2Institut fur Medizinische Biochemie und Molekularbiologie Universitatsklinikum Hamburg-Eppendorf Germany 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 b-sheet and an a-helix a1. We show that the C-terminal portion of MAR-BD also contains an amphipathic helical coil a2 a3. 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. Keywords chicken methyl-CpG-binding protein 2 cMeCP2 MAR-binding protein ARBP NMR spectroscopy protein-DNA interaction. Methylation of the DNA at cytosines in the dinucleotide sequence CpG plays an important role in the regulation of gene expression and imprinting

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