Protein Structure and Folding
Structural basis of the TAM domain of BAZ2A in binding to DNA or RNA independent of methylation status
Bromodomain adjacent to zinc finger domain protein 2A (BAZ2A) (also called transcription termination factor-1 interacting protein 5), a key component of the nucleolar remodeling complex, recruits the nucleolar remodeling complex to ribosomal RNA genes, leading to their transcriptional repression. In addition to its tandem plant homeodomain–bromodomain that is involved in binding to acetylated histone H4, BAZ2A also contains a methyl-CpG–binding domain (MBD)-like Tip5/ARBP/MBD (TAM) domain that shares sequence homology with the MBD.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.
