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

ABSTRACT: 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 (IN_329-408) or its 22-residue IN tail peptide (IN_386-407) alone reveal similar intermolecular three-stranded β-sheet formations. ¹⁵N relaxation studies reveal a 10-residue linker region (IN_379-388) tethering the SH3 domain (IN_329-378) to the ET-binding motif (IN_389-405):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 (NSD3_148-184) and the BRD3 ET domain includes a similar three-stranded β-sheet interaction, but the orientation of the β 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.

SUBMITTER: Aiyer S

PROVIDER: S-EPMC8349776 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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

Aiyer Sriram S Swapna G V T GVT Ma Li-Chung LC Liu Gaohua G Hao Jingzhou J Chalmers Gordon G Jacobs Brian C BC Montelione Gaetano T GT Roth Monica J MJ

Structure (London, England : 1993) 20210215 8

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 β-sheet formations. 15N relaxation studies reveal ...[more]

PMID: 33592170

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Dataset Information

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

Publications

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

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