7QTT
Structural organization of a late activated human spliceosome (Baqr, core region)
Summary for 7QTT
| Entry DOI | 10.2210/pdb7qtt/pdb |
| Related | 5Z57 6FF4 |
| EMDB information | 14146 |
| Descriptor | Splicing factor 3B subunit 3, BUD13 homolog, Putative pre-mRNA-splicing factor ATP-dependent RNA helicase DHX16, ... (41 entities in total) |
| Functional Keywords | spliceosome, helicase, prp2, aquarius, catalytic activation, splicing |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 37 |
| Total formula weight | 2495692.23 |
| Authors | |
| Primary citation | Schmitzova, J.,Cretu, C.,Dienemann, C.,Urlaub, H.,Pena, V. Structural basis of catalytic activation in human splicing. Nature, 617:842-850, 2023 Cited by PubMed Abstract: Pre-mRNA splicing follows a pathway driven by ATP-dependent RNA helicases. A crucial event of the splicing pathway is the catalytic activation, which takes place at the transition between the activated B and the branching-competent B spliceosomes. Catalytic activation occurs through an ATP-dependent remodelling mediated by the helicase PRP2 (also known as DHX16). However, because PRP2 is observed only at the periphery of spliceosomes, its function has remained elusive. Here we show that catalytic activation occurs in two ATP-dependent stages driven by two helicases: PRP2 and Aquarius. The role of Aquarius in splicing has been enigmatic. Here the inactivation of Aquarius leads to the stalling of a spliceosome intermediate-the B complex-found halfway through the catalytic activation process. The cryogenic electron microscopy structure of B reveals how PRP2 and Aquarius remodel B and B, respectively. Notably, PRP2 translocates along the intron while it strips away the RES complex, opens the SF3B1 clamp and unfastens the branch helix. Translocation terminates six nucleotides downstream of the branch site through an assembly of PPIL4, SKIP and the amino-terminal domain of PRP2. Finally, Aquarius enables the dissociation of PRP2, plus the SF3A and SF3B complexes, which promotes the relocation of the branch duplex for catalysis. This work elucidates catalytic activation in human splicing, reveals how a DEAH helicase operates and provides a paradigm for how helicases can coordinate their activities. PubMed: 37165190DOI: 10.1038/s41586-023-06049-w PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.1 Å) |
Structure validation
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