Summary information and primary citation
- PDB-id
-
7w0e;
DSSR-derived features in text and
JSON formats
- Class
- RNA binding protein
- Method
- cryo-EM (4.03 Å)
- Summary
- Dmdicer2-loqspd-dsrna active-dicing status
- Reference
-
Su S, Wang J, Deng T, Yuan X, He J, Liu N, Li X, Huang Y,
Wang HW, Ma J (2022): "Structural
insights into dsRNA processing by Drosophila
Dicer-2-Loqs-PD." Nature,
607, 399-406. doi: 10.1038/s41586-022-04911-x.
- Abstract
- Small interfering RNAs (siRNAs) are the key components
for RNA interference (RNAi), a conserved RNA-silencing
mechanism in many eukaryotes<sub>1,2</sub>. 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)<sub>3,4</sub>.
ATP hydrolysis by the helicase domain of Dcr-2 is critical
to the successful processing of a long dsRNA into
consecutive siRNA duplexes<sub>5,6</sub>. 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.
