7w0c | pdb_00007w0c

Dicer2-Loqs-PD-dsRNA complex at early-translocation state

spinqualitylabelsall models 7w0c, resolution 3.93Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7w0c is a 4 chain structure with sequence from Drosophila melanogaster. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ADP, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [A1ZAW0_DROME] Publication Abstract from PubMed Small interfering RNAs (siRNAs) are the key components for RNA interference (RNAi), a conserved RNA-silencing mechanism in many eukaryotes(1,2). In Drosophila, an RNase III enzyme Dicer-2 (Dcr-2), aided by its cofactor Loquacious-PD (Loqs-PD), has an important role in generating 21 bp siRNA duplexes from long double-stranded RNAs (dsRNAs)(3,4). ATP hydrolysis by the helicase domain of Dcr-2 is critical to the successful processing of a long dsRNA into consecutive siRNA duplexes(5,6). Here we report the cryo-electron microscopy structures of Dcr-2-Loqs-PD in the apo state and in multiple states in which it is processing a 50 bp dsRNA substrate. The structures elucidated interactions between Dcr-2 and Loqs-PD, and substantial conformational changes of Dcr-2 during a dsRNA-processing cycle. The N-terminal helicase and domain of unknown function 283 (DUF283) domains undergo conformational changes after initial dsRNA binding, forming an ATP-binding pocket and a 5'-phosphate-binding pocket. The overall conformation of Dcr-2-Loqs-PD is relatively rigid during translocating along the dsRNA in the presence of ATP, whereas the interactions between the DUF283 and RIIIDb domains prevent non-specific cleavage during translocation by blocking the access of dsRNA to the RNase active centre. Additional ATP-dependent conformational changes are required to form an active dicing state and precisely cleave the dsRNA into a 21 bp siRNA duplex as confirmed by the structure in the post-dicing state. Collectively, this study revealed the molecular mechanism for the full cycle of ATP-dependent dsRNA processing by Dcr-2-Loqs-PD. Structural insights into dsRNA processing by Drosophila Dicer-2-Loqs-PD.,Su S, Wang J, Deng T, Yuan X, He J, Liu N, Li X, Huang Y, Wang HW, Ma J Nature. 2022 Jul;607(7918):399-406. doi: 10.1038/s41586-022-04911-x. Epub 2022, Jun 29. PMID:35768513 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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