8I0W

The cryo-EM structure of human C complex

This is a non-PDB format compatible entry.

Summary for 8I0W

• Entry DOI: 10.2210/pdb8i0w/pdb
• EMDB information: 35113
• Descriptor: Pre-mRNA-processing-splicing factor 8, Pre-mRNA-splicing factor SYF1, Crooked neck-like protein 1, ... (52 entities in total)
• Functional Keywords: spliceosome, rna splicing, prp16, branching, splicing
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 58
• Total formula weight: 3241207.90

Authors

Zhan, X.,Lu, Y.,Shi, Y. (deposition date: 2023-01-11, release date: 2024-07-31, Last modification date: 2024-10-16)

Primary citation

Zhan, X.,Lu, Y.,Shi, Y.
Molecular basis for the activation of human spliceosome.
Nat Commun, 15:6348-6348, 2024

PubMed 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 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, B-I, B-II, B-III, B-IV, and post-B. 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.

PubMed: 39068178
DOI: 10.1038/s41467-024-50785-0

Experimental method

ELECTRON MICROSCOPY (3.4 Å)