Figure 7.

Including 2′-O-Methyl at the 3′ End of an siRNA Guide Strand May Disrupt Its Anchoring in Ago2-PAZ

(A) Legend shows corresponding chemical structures for 3′ end 2′-ribose chemistries. (B) Crystal structure of the Drosophila Ago-PAZ domain (yellow), loaded with a 9-mer small RNA (black) with 2′-OMe at its 3′ end. Image also includes a 21-mer unmodified siRNA guide strand (raspberry). The distances between the 3′ ends of each small RNA and the closest residue in Drosophila Ago (LEU707) are shown. (C) Crystal structure of human Ago2-PAZ (deep teal), loaded with a 21-mer unmodified siRNA guide strand (light pink). Image also includes a 9-mer small RNA (black) with 2′-OMe at its 3′ end. The distances between the 3′ ends of each small RNA and the closest residue in Ago2 (TYR338) are shown. (D) Crystal structure of human Ago2-PAZ (deep teal), loaded with a 21-mer unmodified siRNA guide strand (light pink) showing positions 20 and 21 anchored into the binding pocket of the PAZ domain.