One form and two functions: MBD of SETDB2 is a protein-interacting domain

In this issue of Structure, Mahana et al. 1 Mahana Y. Ariyoshi M. Nozawa R.S. Shibata S. Nagao K. Obuse C. Shirakawa M. Structural evidence for protein-protein interaction between the non-canonical methyl-CpG-binding domain of SETDB proteins and C11orf46. Structure. 2023; 32: 304-315https://doi.org/10.1016/j.str.2023.12.001 Abstract Full Text Full Text PDF Scopus (1) Google Scholar present their structural characterization of an annotated methyl-CpG-binding domain (MBD) from the histone H3 lysine 9 methyltransferase SETDB2. This study reveals that, rather than binding DNA as previously hypothesized, this domain instead interacts with a cystine-rich domain from C11orf46, highlighting its involvement in protein-protein interactions. In this issue of Structure, Mahana et al. 1 Mahana Y. Ariyoshi M. Nozawa R.S. Shibata S. Nagao K. Obuse C. Shirakawa M. Structural evidence for protein-protein interaction between the non-canonical methyl-CpG-binding domain of SETDB proteins and C11orf46. Structure. 2023; 32: 304-315https://doi.org/10.1016/j.str.2023.12.001 Abstract Full Text Full Text PDF Scopus (1) Google Scholar present their structural characterization of an annotated methyl-CpG-binding domain (MBD) from the histone H3 lysine 9 methyltransferase SETDB2. This study reveals that, rather than binding DNA as previously hypothesized, this domain instead interacts with a cystine-rich domain from C11orf46, highlighting its involvement in protein-protein interactions. Structural evidence for protein-protein interaction between the non-canonical methyl-CpG-binding domain of SETDB proteins and C11orf46Mahana et al.StructureDecember 29, 2023In BriefC11orf46 has been identified in SETDB-associated repression complexes. Mahana et al. demonstrate that the non-canonical MBD of SETDB2, despite its conserved MBD architecture, mediates a protein-protein interaction with C11orf46 CRD rather than methylated DNA binding. This finding highlights the diverse functional roles of MBDs in transcriptional repression. Full-Text PDF