5ZAL

Cryo-EM structure of human Dicer and its complexes with a pre-miRNA substrate

5ZAL の概要

• エントリーDOI: 10.2210/pdb5zal/pdb
• EMDBエントリー: 6905
• 分子名称: Endoribonuclease Dicer, RISC-loading complex subunit TARBP2, RNA (73-mer) (3 entities in total)
• 機能のキーワード: dicer, trbp, cryo-em, rna interference, protein binding, hydrolase-protein binding-rna complex, hydrolase/protein binding/rna
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 281408.43

構造登録者

Liu, Z.,Wang, J.,Cheng, H.,Ke, X.,Sun, L.,Zhang, Q.C.,Wang, H.-W. (登録日: 2018-02-07, 公開日: 2018-05-09, 最終更新日: 2024-10-16)

主引用文献

Liu, Z.,Wang, J.,Cheng, H.,Ke, X.,Sun, L.,Zhang, Q.C.,Wang, H.W.
Cryo-EM Structure of Human Dicer and Its Complexes with a Pre-miRNA Substrate.
Cell, 173:1191-1203.e12, 2018

PubMed Abstract: Human Dicer (hDicer) is a multi-domain protein belonging to the RNase III family. It plays pivotal roles in small RNA biogenesis during the RNA interference (RNAi) pathway by processing a diverse range of double-stranded RNA (dsRNA) precursors to generate ∼22 nt microRNA (miRNA) or small interfering RNA (siRNA) products for sequence-directed gene silencing. In this work, we solved the cryoelectron microscopy (cryo-EM) structure of hDicer in complex with its cofactor protein TRBP and revealed the precise spatial arrangement of hDicer's multiple domains. We further solved structures of the hDicer-TRBP complex bound with pre-let-7 RNA in two distinct conformations. In combination with biochemical analysis, these structures reveal a property of the hDicer-TRBP complex to promote the stability of pre-miRNA's stem duplex in a pre-dicing state. These results provide insights into the mechanism of RNA processing by hDicer and illustrate the regulatory role of hDicer's N-terminal helicase domain.

PubMed: 29706542
DOI: 10.1016/j.cell.2018.03.080

実験手法

ELECTRON MICROSCOPY (4.7 Å)