EMD-35110

Single-particle
3.3 Å
EMD-35110 Deposition: 11/01/2023
Map released: 31/07/2024
Last modified: 23/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-35110

The cryo-EM structure of human Bact-IV complex

EMD-35110

Single-particle
3.3 Å
EMD-35110 Deposition: 11/01/2023
Map released: 31/07/2024
Last modified: 23/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens
Sample: The human Bact-III complex
Fitted models: 8i0u (Avg. Q-score: 0.195)

Deposition Authors: Zhan X , Lu Y, Shi Y
Molecular basis for the activation of human spliceosome.
Zhan X , Lu Y, Shi Y
(2024) Nat Commun , 15 , 6348 - 6348
PUBMED: 39068178
DOI: doi:10.1038/s41467-024-50785-0
ISSN: 2041-1723
Abstract:
The spliceosome executes pre-mRNA splicing through four sequential stages: assembly, activation, catalysis, and disassembly. Activation of the spliceosome, namely remodeling of the pre-catalytic spliceosome (B complex) into the activated spliceosome (Bact complex) and the catalytically activated spliceosome (B* complex), involves major flux of protein components and structural rearrangements. Relying on a splicing inhibitor, we have captured six intermediate states between the B and B* complexes: pre-Bact, Bact-I, Bact-II, Bact-III, Bact-IV, and post-Bact. Their cryo-EM structures, together with an improved structure of the catalytic step I spliceosome (C complex), reveal how the catalytic center matures around the internal stem loop of U6 snRNA, how the branch site approaches 5'-splice site, how the RNA helicase PRP2 rearranges to bind pre-mRNA, and how U2 snRNP undergoes remarkable movement to facilitate activation. We identify a previously unrecognized key role of PRP2 in spliceosome activation. Our study recapitulates a molecular choreography of the human spliceosome during its catalytic activation.