8yzt | pdb_00008yzt
Crystal structure of the BANP BEN domain in complex with its target DNA
Structural highlights
FunctionBANP_HUMAN Controls V(D)J recombination during T-cell development by repressing T-cell receptor (TCR) beta enhancer function. Binds to scaffold/matrix attachment region beta (S/MARbeta), an ATC-rich DNA sequence located upstream of the TCR beta enhancer. Represses cyclin D1 transcription by recruiting HDAC1 to its promoter, thereby diminishing H3K9ac, H3S10ph and H4K8ac levels. Promotes TP53 activation, which causes cell cycle arrest (By similarity).[UniProtKB:Q8VBU8][1] Publication Abstract from PubMedThe BEN domain is a newly discovered type of DNA-binding domain that exists in a variety of species. There are nine BEN domain-containing proteins in humans, and most have been shown to have chromatin-related functions. NACC1 preferentially binds to CATG motif-containing sequences and functions primarily as a transcriptional coregulator. BANP and BEND3 preferentially bind DNA bearing unmethylated CpG motifs, and they function as CpG island-binding proteins. To date, the DNA recognition mechanism of quite a few of these proteins remains to be determined. In this study, we solved the crystal structures of the BEN domains of NACC1 and BANP in complex with their cognate DNA substrates. We revealed the details of DNA binding by these BEN domain proteins and unexpectedly revealed that oligomerization is required for BANP to select unmethylated CGCG motif-containing DNA substrates. Our study clarifies the controversies surrounding DNA recognition by BANP and demonstrates a new mechanism by which BANP selects unmethylated CpG motifs and functions as a CpG island-binding protein. This understanding will facilitate further exploration of the physiological functions of the BEN domain proteins in the future. Structural basis of DNA recognition by BEN domain proteins reveals a role for oligomerization in unmethylated DNA selection by BANP.,Ren J, Wang J, Ren Y, Zhang Y, Wei P, Wang M, Zhang Y, Li M, Yuan C, Gong H, Jiang J, Wang Z Nucleic Acids Res. 2024 Sep 3:gkae762. doi: 10.1093/nar/gkae762. PMID:39225042[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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