A common binding motif in the ET domain of BRD3 forms polymorphic structural interfaces with host and viral proteins

The extraterminal (ET) domain of BRD3 is conserved among BET proteins (BRD2, BRD3, BRD4), interacting with multiple host and viral protein-protein networks. Solution NMR structures of complexes formed between the BRD3 ET domain and either the 79-residue murine leukemia virus integrase (IN) C-terminal domain (IN329-408) or its 22-residue IN tail peptide (IN386-407) alone reveal similar intermolecular three-stranded beta-sheet formations. N-15 relaxation studies reveal a 10-residue linker region (IN379-388) tethering the SH3 domain (IN329-378) to the ET-binding motif (IN389-405):ET complex. This linker has restricted flexibility, affecting its potential range of orientations in the IN:nucleosome complex. The complex of the ET-binding peptide of the host NSD3 protein (NSD3148-184) and the BRD3 ET domain includes a similar three-stranded beta-sheet interaction, but the orientation of the beta hairpin is flipped compared with the two IN:ET complexes. These studies expand our understanding of molecular recognition polymorphism in complexes of ET-binding motifs with viral and host proteins.

Automated summary

The ET domain of BRD3 interacts with viral and host proteins through similar beta-sheet formations. N-15 relaxation studies reveal a restricted flexibility in the linker region, affecting its orientation in the protein complexes. The complex of the ET-binding peptide of host NSD3 protein and the BRD3 ET domain shows a different orientation compared to viral protein complexes.