Protein Structure and Folding
Structural basis for the ability of MBD domains to bind methyl-CG and TG sites in DNA
Cytosine methylation is a well-characterized epigenetic mark and occurs at both CG and non-CG sites in DNA. Both methylated CG (mCG)- and mCH (H = A, C, or T)-containing DNAs, especially mCAC-containing DNAs, are recognized by methyl-CpG–binding protein 2 (MeCP2) to regulate gene expression in neuron development. However, the molecular mechanism involved in the binding of methyl-CpG–binding domain (MBD) of MeCP2 to these different DNA motifs is unclear. Here, we systematically characterized the DNA-binding selectivities of the MBD domains in MeCP2 and MBD1–4 with isothermal titration calorimetry–based binding assays, mutagenesis studies, and X-ray crystallography.Structural Basis for the Discriminative Recognition of N6-Methyladenosine RNA by the Human YT521-B Homology Domain Family of Proteins
Background: Human YT521-B homology (YTH) domain selectively recognizes N6-methyladenosine (m6A) RNA.Results: YTHDF1 and Pho92 recognize m6A without sequence preference.Conclusion: The structure of YTHDF1 explained the key residue difference that results in the weaker binding of YTHDF1-3 compared with YTHDC1.Significance: This study systematically investigated the binding characteristics of the human YTH domain proteins, as well as yeast Pho92, and indicated the discriminative recognition of m6A among different YTH domains.
