Solution structure of the matrix attachment region-binding domain of chicken MeCP2.
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 alpha1. We show that the C-terminal portion of MAR-BD also contains an amphipathic helical coil, alpha2/alpha3. 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.
Heitmann
Björn
B
Institut für Biophysik und physikalische Biochemie, Universität Regensburg, Germany.
Maurer
Till
T
Weitzel
Joachim M
JM
Strätling
Wolf H
WH
Kalbitzer
Hans Robert
HR
Brunner
Eike
E
D000818:Animals; D001665:Binding Sites; D002645:Chickens; D002868:Chromosomal Proteins, Non-Histone; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051783:Methyl-CpG-Binding Protein 2; D008958:Models, Molecular; D009154:Mutation; D019906:Nuclear Magnetic Resonance, Biomolecular; D015530:Nuclear Matrix / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins; D015518:Rett Syndrome / Q000235:genetics
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D051783:Methyl-CpG-Binding Protein 2; D012097:Repressor Proteins; D004247:DNA