Comparison of Ago2 structure model to EIF4e cap-binding mode. (A) A ribbon diagram depicts the Ago2 mid domain homology-based structure model (2bgg template). The distance between labeled aromatic residue (magenta stick) C-alpha carbons is indicated. Locally similar structure elements (to eIF4E) surrounding these residues are colored pink, with the remaining MC region colored light blue. Conserved residues (black stick) form hydrogen bonds (dashed lines) to the 5'phosphate of guide RNA (slate). (B) A ribbon diagram illustrates the eIF4E cap-binding mode (1l8b). M7G stacks between labeled aromatic residues (magenta stick) and forms hydrogen bonds to additional conserved residues (black stick). Cap-binding motif corresponding to MC region is colored and depicted as in (A). (C) and (D) Ago2 aromatic residue surroundings (1w9h template) are zoomed in around the C-alpha position of F450 (C) or F505 (D). Neighboring residues are rendered as sticks, colored as above, and labeled with corresponding Ago2 numbering. (E) A zoom of the piwi (2bgg) guide RNA 5'nucleotide-binding pocket. Conserved residues (black stick) that hydrogen bond (dashed lines) to nucleotide (ball and stick) phosphates or stack with the 5' nucleotide base are labeled according to the corresponding Ago2 residues. A divalent cation (purple sphere) is found between the 5' phosphate and a phosphate from the third guide RNA nucleotide. (F) A zoom of the eIF4e cap-binding pocket (1l8b) with the m7Gppp cap analog oriented similarly to the piwi 5'guide RNA nucleotide to illustrate similarities. Conserved eIF4e residues (black stick) that hydrogen bond to nucleotide phosphates and stack with the nucleotide base are labeled.