8ch6 | pdb_00008ch6

Structure of a late-stage activated spliceosome (BAqr) arrested with a dominant-negative Aquarius mutant (state B complex).

spinqualitylabelsall models 8ch6, resolution 5.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8ch6 is a 17 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 5.9Å Ligands: GTP, IHP, MG, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RUXE_HUMAN Appears to function in the U7 snRNP complex that is involved in histone 3'-end processing. Associated with snRNP U1, U2, U4/U6 and U5. Publication Abstract from PubMed 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(act) and the branching-competent B(*) spliceosomes. Catalytic activation occurs through an ATP-dependent remodelling mediated by the helicase PRP2 (also known as DHX16)(1-3). However, because PRP2 is observed only at the periphery of spliceosomes(3-5), 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(6,7). Here the inactivation of Aquarius leads to the stalling of a spliceosome intermediate-the B(AQR) complex-found halfway through the catalytic activation process. The cryogenic electron microscopy structure of B(AQR) reveals how PRP2 and Aquarius remodel B(act) and B(AQR), 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. Structural basis of catalytic activation in human splicing.,Schmitzova J, Cretu C, Dienemann C, Urlaub H, Pena V Nature. 2023 May;617(7962):842-850. doi: 10.1038/s41586-023-06049-w. Epub 2023 , May 10. PMID:37165190 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Nucleoprotein 3D structures Pre-mRNA splicing factors 3D structures

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