7ZPK
Mammalian Dicer in the "pre-dicing state" with pre-miR-15a substrate and TARBP2 subunit
Summary for 7ZPK
| Entry DOI | 10.2210/pdb7zpk/pdb |
| EMDB information | 14383 14384 14387 14856 |
| Descriptor | Endoribonuclease Dicer, 59-nt precursor of miR-15a, RISC-loading complex subunit TARBP2 (3 entities in total) |
| Functional Keywords | endoribonuclease, dsrna, complex, gene silencing, post-transcriptional, catalytic complex, cytoplasm, risc-loading complex, tarbp2 rna binding protein, rna binding protein |
| Biological source | Mus musculus (house mouse) More |
| Total number of polymer chains | 3 |
| Total formula weight | 285933.99 |
| Authors | Zanova, M.,Zapletal, D.,Kubicek, K.,Stefl, R.,Pinkas, M.,Novacek, J. (deposition date: 2022-04-27, release date: 2022-11-16, Last modification date: 2024-07-24) |
| Primary citation | Zapletal, D.,Taborska, E.,Pasulka, J.,Malik, R.,Kubicek, K.,Zanova, M.,Much, C.,Sebesta, M.,Buccheri, V.,Horvat, F.,Jenickova, I.,Prochazkova, M.,Prochazka, J.,Pinkas, M.,Novacek, J.,Joseph, D.F.,Sedlacek, R.,Bernecky, C.,O'Carroll, D.,Stefl, R.,Svoboda, P. Structural and functional basis of mammalian microRNA biogenesis by Dicer. Mol.Cell, 82:4064-4079.e13, 2022 Cited by PubMed Abstract: MicroRNA (miRNA) and RNA interference (RNAi) pathways rely on small RNAs produced by Dicer endonucleases. Mammalian Dicer primarily supports the essential gene-regulating miRNA pathway, but how it is specifically adapted to miRNA biogenesis is unknown. We show that the adaptation entails a unique structural role of Dicer's DExD/H helicase domain. Although mice tolerate loss of its putative ATPase function, the complete absence of the domain is lethal because it assures high-fidelity miRNA biogenesis. Structures of murine Dicer•-miRNA precursor complexes revealed that the DExD/H domain has a helicase-unrelated structural function. It locks Dicer in a closed state, which facilitates miRNA precursor selection. Transition to a cleavage-competent open state is stimulated by Dicer-binding protein TARBP2. Absence of the DExD/H domain or its mutations unlocks the closed state, reduces substrate selectivity, and activates RNAi. Thus, the DExD/H domain structurally contributes to mammalian miRNA biogenesis and underlies mechanistical partitioning of miRNA and RNAi pathways. PubMed: 36332606DOI: 10.1016/j.molcel.2022.10.010 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.81 Å) |
Structure validation
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