PXD033365
PXD033365 is an original dataset announced via ProteomeXchange.
Dataset Summary
Title | Structural insights into dsRNA processing by Drosophila Dicer-2/Loqs-PD |
Description | Small interfering RNAs (siRNAs) are the key components for RNA interference (RNAi), a conserved RNA silencing mechanism in many eukaryotes. In Drosophila, an RNase III enzyme Dicer-2 (Dcr-2), aided by its cofactor Loquacious-PD (Loqs-PD), plays major role in generating 21 base-pair (bp) siRNA duplexes from long double-stranded RNAs (dsRNAs). The ATP hydrolysis by the helicase domain of Dcr-2 is critical to the successful processing of a long dsRNA into consecutive siRNA duplexes. Here we report the cryo-EM structures of Dcr-2/Loqs-PD in the apo state and in multiple processing states of a 50-bp dsRNA substrate. The structures elucidated interactions between Dcr-2 and Loqs-PD, and significant conformational changes of Dcr-2 during a dsRNA processing cycle. The N-terminal helicase and DUF283 domains undergo conformational change upon 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, while the interaction between DUF283 and RIIIDb domains prevents non-specific cleavage during translocation by blocking the access of dsRNA to the RNase active center. Additional ATP-dependent conformational changes are required to form an active-dicing state and precisely cleave the dsRNA into 21-bp siRNA duplex 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. |
HostingRepository | iProX |
AnnounceDate | 2022-04-21 |
AnnouncementXML | Submission_2023-12-25_20:04:55.273.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Chenshi Su |
SpeciesList | scientific name: Drosophila melanogaster; NCBI TaxID: 7227; |
ModificationList | No PTMs are included in the dataset |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2022-04-21 19:21:32 | ID requested | |
1 | 2022-04-21 19:21:48 | announced | |
⏵ 2 | 2023-12-25 20:04:56 | announced | 2023-12-26: Update information. |
Publication List
Keyword List
submitter keyword: RNAi, siRNA processing, ATP-dependent RNA helicase, Dicer-2, Loqs-PD |
Contact List
Jinbiao Ma | |
---|---|
contact affiliation | Department of Biochemistry and Biophysics, School of Life Sciences, Fudan University |
contact email | majb@fudan.edu.cn |
lab head | |
Chenshi Su | |
contact affiliation | Department of Biochemistry and Biophysics, School of Life Sciences, Fudan University |
contact email | scsu15@fudan.edu.cn |
dataset submitter |
Full Dataset Link List
iProX dataset URI |