Fig. 12

Molecular modeling of the binding of 14-3-3θ homodimer to Eag1. Protein docking models based on the structures of human 14-3-3θ (PDB: 2BTP) and rat Eag1 (PDB: 5K7L). A Ribbon representation of a single 14-3-3θ homodimer (colored in aqua and green) interacting with the N-linker region (raspberry) and PAS domain (violet) of one Eag1 subunit, the proximal CNBHD (burgundy) of a second Eag1 subunit, and the proximal post-CNBHD region (blue) of a third Eag1 subunit. The PAS domain (violet) from one Eag1 subunit directly interacts with the distal end of the CNBHD (burgundy) of a neighboring Eag1 subunit, with the intrinsic ligand motif (YNL) emphasized in lime. A portion of the distal segment of the post-CNBHD region (blue), which may also be in contact with 14-3-3, is schematically presented as spheres. The two yellow boxes (~ 15 Å × 15 Å) denote the 14-3-3θ-Eag1 binding regions highlighted in (B) and (C). B Enlarged view of the 14-3-3θ-Eag1 binding region enclosed by the yellow box to the left in (A), highlighting that the H4, H5, and H6 helices (aqua) of the same 14-3-3θ subunit are in close proximity (~ 3–5 Å) with the N-linker (raspberry) of Eag1. Specific residues in 14-3-3θ and Eag1 are labeled in aqua and raspberry, respectively. C Enlarged view of the 14-3-3θ-Eag1 binding region enclosed by the yellow box to the right in (A), highlighting that the H1 helix (aqua) from one 14-3-3θ subunit and the H3 helix (green) from the other 14-3-3θ subunit are in close proximity (~ 3–5 Å) with the proximal CNBHD (burgundy) of Eag1. Specific residues in the two 14-3-3θ subunits are labeled in aqua and green, respectively. D Intracellular view of four 14-3-3θ homodimers (all in aqua and green) in contact with the Eag1 tetramer (violet, burgundy, blue, salmon). CNBHDs are located in the center region, directly interacting with PAS domains from neighboring Eag1 subunits