Graphical illustration of amino acid residues
at the MLV IN EBM-Brd4
ET domain interaction interface. (A) Schematic representation of MLV
integrase (IN) and Brd4 (1–1342). Key domains and structural
features are indicated for both: MLV IN C-terminal domain (CTD), catalytic
core domain (CCD), and N-terminal domain (NTD). The ET-binding motif
(EBM) is indicated in orange, and the location of LKIRL is highlighted
in red. Brd4 bromodomains (BD1 and BD2), DNA binding motifs A and
B, SEED domain, and extra-terminal domain (ET). (B) Representation
of amino acids residue in the β6′ strand of EBM (pink)
and their interaction with the Brd4 ET domain (blue). Two perspectives
of view indicate that the highlighted residues are not extensively
in contact with the ET domain. (C) Annotation of the secondary structure
of the EBM β-sheet and ET domain (PDB Code: 2N3K). (D) MM/GBSA per-residue
energy decomposition profile of the EBM-ET complex indicating that
β7′ of EBM and β1 of ET predominantly contribute
to the protein–protein interaction. (E) Binding mode of LKIRL
(399′–403′) with the ET domain showing that the
LKIRL sequence interacts extensively with β1 of ET.