Figure 2.

Structure and molecular details of Cm eIF4E unbound or bound to Cm eIF4G_1003-1092. A, Ribbon diagram of Cm eIF4E_51-235 in complex with the m⁷GDP cap analog. The m⁷GDP is located in the cap-binding pocket. Residue W128, in direct interaction with the cap, is marked. B and C, Structure of the Cm eIF4E-eIF4G_1003-1092 complex shown as a cartoon and surface rendering, respectively. Cm eIF4G_1003-1092 (orange) contains the C and NC eIF4E binding motifs (4E-BM). D, Structural superposition of Cm eIF4E (in gray as cartoon) and Cm eIF4E-eIF4G_1003-1092 (in blue as cartoon) binding pocket structures. The formation of a disulfide bridge (shown as sticks in yellow in the structure) promotes the formation of a helix 3₁₀ in loop L3 and pulls W128 from m⁷GDP-interacting position 1 to an apparently “auto-inhibited” position 2 (both labeled in the figure). E, Close-up views of the interaction of the Cm eIF4G C motif (orange) with the dorsal surface of Cm eIF4E (blue) in two orientations. F, Close-up view of the Cm eIF4G linker region (orange) and interactions with Cm eIF4E (blue). G, Close-up view of the NC interaction loop of Cm eIF4G (orange) showing all interactions with the lateral surface of Cm eIF4E (blue). Selected interface residues are shown as blue sticks for Cm eIF4E and as orange sticks for Cm eIF4G. In E to G, residues implicated in the interactions between Cm eIF4E and Cm eIF4G_1003-1092 are shown as sticks.