SNAP annotations: PDB entry 8i0s

PDB-id

8i0s; DSSR-derived features in text and JSON formats; DNAproDB

Class

splicing

Method

cryo-EM (4.2 Å)

Summary

The cryo-EM structure of human bact-ii complex

Reference

Zhan X, Lu Y, Shi Y (2024): "Molecular basis for the activation of human spliceosome." Nat Commun, 15, 6348. doi: 10.1038/s41467-024-50785-0.

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 (B_act 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-B_act, B_act-I, B_act-II, B_act-III, B_act-IV, and post-B_act. 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.