2. Academic Validation
  3. Structure and Conformational Dynamics of the Human Spliceosomal Bact Complex

Structure and Conformational Dynamics of the Human Spliceosomal Bact Complex

  • Cell. 2018 Jan 25;172(3):454-464.e11. doi: 10.1016/j.cell.2018.01.010.
David Haselbach 1,  Ilya Komarov 2,  Dmitry E Agafonov 2,  Klaus Hartmuth 2,  Benjamin Graf 1,  Olexandr Dybkov 2,  Henning Urlaub 3,  Berthold Kastner 2,  Reinhard Lührmann 4,  Holger Stark 5
Affiliations

Affiliations

  • 1 Department for Structural Dynamics, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
  • 2 Department for Cellular Biochemistry, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
  • 3 Bioanalytic Mass Spectrometry Group, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany; Bioanalytics Group, Institute for Clinical Chemistry, University Medical Center Göttingen, Robert-Koch-Str. 40, 37073 Göttingen, Germany.
  • 4 Department for Cellular Biochemistry, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany. Electronic address: reinhard.luehrmann@mpi-bpc.mpg.de.
  • 5 Department for Structural Dynamics, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany. Electronic address: hstark1@gwdg.de.
PMID: 29361316 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 Bact spliceosome at 3.4 Å resolution. In the Bact 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 Bact 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.

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