SNAP output for PDB entry 6ff7 [SNAP web server]

PDB-id

6ff7; SNAP-derived features in text and JSON formats; DNAproDB

Class

splicing

Method

cryo-EM (4.5 Å)

Summary

Human bact spliceosome core structure

Reference

Haselbach D, Komarov I, Agafonov DE, Hartmuth K, Graf B, Dybkov O, Urlaub H, Kastner B, Luhrmann R, Stark H (2018): "Structure and Conformational Dynamics of the Human Spliceosomal BactComplex." Cell, 172, 454-464.e11. doi: 10.1016/j.cell.2018.01.010.

Abstract

The spliceosome is a highly dynamic macromolecular complex that precisely excises introns from pre-mRNA. Here we report the cryo-EM 3D structure of the human B_act spliceosome at 3.4 Å resolution. In the B_act state, the spliceosome is activated but not catalytically primed, so that it is functionally blocked prior to the first catalytic step of splicing. The spliceosomal core is similar to the yeast B_act spliceosome; important differences include the presence of the RNA helicase aquarius and peptidyl prolyl isomerases. To examine the overall dynamic behavior of the purified spliceosome, we developed a principal component analysis-based approach. Calculating the energy landscape revealed eight major conformational states, which we refined to higher resolution. Conformational differences of the highly flexible structural components between these eight states reveal how spliceosomal components contribute to the assembly of the spliceosome, allowing it to generate a dynamic interaction network required for its subsequent catalytic activation.