Drosha/Dicer/Ago2 and PACT/TRBP. (a) Domain architectures and structures of human Drosha, Dicer, and Ago2. The structures of human Dicer (PDB: 5ZAL and 4NHA) in complex with dsRNA showed two distinct conformations representing the preslicing mode (where dsRNA is far from the slicing center) and the slicing mode (where dsRNA contacts the slicing center). dsRNA in the slicing mode was modeled based on the structure of Dicer platform-PAZ in complex with dsRNA (PDB:4NHA). Note that in the preslicing conformation, the helicase domain (green) interacts with dsRNA in a manner distinct from the RLR helicase domains. By contrast, the structure of Drosophila Dicer-2 (PDB: 6BU9, right) shows that the Dicer helicase domain partially encircles dsRNA, similarly to the RLR helicase domains. (b) Domain architectures and structures of PACT and TRBP. The structures of canonical dsRBD1–2 of TRBP in complex with dsRNA (PDB: 5N8M) and noncanonical dsRBD3 in complex with Dicer Hel2i (PDB: 4WYQ). The overlay of the two structures on the right shows that noncanonical dsRBD3 is structurally similar to canonical dsRBDs. Abbreviations: dsRBD, dsRNA-binding domain; RLR, RIG-I-like receptor.