title: Recognition of methylated DNA through methyl-CpG binding domain proteins.
abstract: DNA methylation is a key regulatory control route in epigenetics, involving gene silencing and chromosome inactivation. It has been recognized that methyl-CpG binding domain (MBD) proteins play an important role in interpreting the genetic information encoded by methylated DNA (mDNA). Although the function of MBD proteins has attracted considerable attention and is well characterized, the mechanism underlying mDNA recognition by MBD proteins is still poorly understood. In this article, we demonstrate that the methyl-CpG dinucleotides are recognized at the MBD-mDNA interface by two MBD arginines through an interplay of hydrogen bonding and cation-π interaction. Through molecular dynamics and quantum-chemistry calculations we investigate the methyl-cytosine recognition process and demonstrate that methylation enhances MBD-mDNA binding by increasing the hydrophobic interfacial area and by strengthening the interaction between mDNA and MBD proteins. Free-energy perturbation calculations also show that methylation yields favorable contribution to the binding free energy for MBD-mDNA complex.
authors: Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
authors: Xueqing
authors: X
authors: Zou
authors: Wen
authors: W
authors: Ma
authors: Ilia A
authors: IA
authors: Solov'yov
authors: Christophe
authors: C
authors: Chipot
authors: Klaus
authors: K
authors: Schulten
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000737:chemistry; D004247:DNA / Q000737:chemistry*; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000737:chemistry; D051379:Mice; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C066141:MBD1 protein, human; C115368:MBD2 protein; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D014157:Transcription Factors; D004247:DNA; D001120:Arginine