FIGURE 1.

Structure of RXRαLBD-SMRT. A, overall architecture of RXRαLBD-SMRT. Each RXRαLBD monomer and SMRT peptide is shown in a distinct color. B, RXRαLBD monomer indicating the key secondary structures for activation. wheat, conserved RXRαLBD core structure; green, N-terminal helix 3; yellow, helix 11; cyan, C-terminal AF-2 motif; blue, neighboring AF-2 motif; red, SMRT. Ligand-binding pockets are also indicated in the gray cycle. C, comparison of the tetramer rotations between the RXRαLBD-SMRT on the left and apoRXRαLBD on the right. Rotations are shown in both ribbon (upper) and model (lower) configurations. D, Ile⁴⁴² and Thr⁴⁴⁴ forming two hydrogen bonds with Arg³⁴⁸ and Arg³⁰² of the two neighboring monomers, respectively. E, Phe⁴³⁷ and Phe⁴³⁸ in the four monomers making hydrophobic interactions with each other in a hand-in-hand manner. Leu⁴⁴¹ of each monomer extends itself inward to further stabilize helix 11 hydrophobically. F, structural superposition among apoRXRαLBD (blue), SMRT-bound RXRαLBD (red), and agonist-activated RXRαLBD (cyan) structures revealing different conformations of helix 3 and AF-2. The conserved core structure of the LBD is shown as surface; coactivator SRC-1 is in green, corepressor SMRT in yellow, and the AF-2 motif of the neighboring monomer in magenta. G, interactions between the SMRT motif (cylinder) and RXRαLBD (boxed residues, helix 3 in blue, helix 5 in green, and the AF-2 motif of the neighboring monomer in red). H, structure-based sequence alignment of the AF-2 motif, corepressor SMRT, and coactivator SRC1 on the overlapped binding pocket. The key residues are shown in red boxes and are indicated for the agonist or antagonist binding.