Extended Data Fig. 5: RIIID insertions interact with the regulatory regions of Dcr-2 and participate in dimer formation of the initial binding state.

a, Overview of inter-region interactions of RIIIDai and RIIIDbi. Hel2, Hel2i, and C-terminal dsRBD are hidden in this panel. The core region except for the C-terminal dsRBD is shown in a cartoon model. Other parts of Dcr-2 is shown in transparent surface. b, Inter-region contacts of RIIIDai and the cap region, corresponding to the orange box in (a). The interactions between RIIIDai and the cap region are mainly hydrophobic. The residues involved in the interactions are shown as sticks. Cyan dashes represent the hydrogen bonds. c, Inter-region contacts of RIIIDb and RIIIDbi with the base region, corresponding to the cyan box in (a). The interactions between them are mainly hydrophilic. Residues and hydrogen bonds are marked as in (c). d, The EM density of aa 1273–1286 of RIIIDai domain with the fitted atomic model. e, Two different views of Dcr-2’s core region in the apo-state. The RNase active centre is marked with black dotted circles and the corresponding residues in the cartoon was labelled in red colour. f, Details of interactions at the dimer interface of the initial binding state. The interactions between RIIIDai and helicase domain are mainly hydrophilic. The residues involved in the interactions are shown as sticks. Cyan dashes represent the hydrogen bonds. g, The EM density of aa 1325–1339 of RIIIDai domain with fitted atomic models. h, Schematic summary of the inter-molecule cross-linking residues in the dimer of initial binding state from XL-MS result. The BS3 and EDC cross-linking sites are coloured in blue and red, respectively. i, The table of distance between cross-linking residues in monomer state or in dimer state. j, Close-up view of inter-molecule BS3 and EDC cross-linking residues in the initial binding state. The cross-linking site is coloured as in (h). k, Overlay view of the size exclusion chromatography results of Dcr-2^WT, Dcr-2^R1330A, and Dcr-2^{R1308A/R1309A/R1330A} with Loqs-PD and dsRNA.