Download MendeleyMolecular architecture of the Saccharomyces cerevisiae activated spliceosome
Rauhut, R., Fabrizio, P., Dybkov, O., Hartmuth, K., Pena, V., Chari, A., Kumar, V., Lee, C.T., Urlaub, H., Kastner, B., Stark, H., Luehrmann, R.(2016) Science 6306: 1399-1405
- PubMed: 27562955
- DOI: https://doi.org/10.1126/science.aag1906
- Primary Citation of Related Structures:
5LQW - PubMed Abstract:
The activated spliceosome (B act ) is in a catalytically inactive state and is remodeled into a catalytically active machine by the RNA helicase Prp2, but the mechanism is unclear. Here, we describe a 3D electron cryomicroscopy structure of the Saccharomyces cerevisiae B act complex at 5.8-angstrom resolution. Our model reveals that in B act , the catalytic U2/U6 RNA-Prp8 ribonucleoprotein core is already established, and the 5' splice site (ss) is oriented for step 1 catalysis but occluded by protein. The first-step nucleophile-the branchsite adenosine-is sequestered within the Hsh155 HEAT domain and is held 50 angstroms away from the 5'ss. Our structure suggests that Prp2 adenosine triphosphatase-mediated remodeling leads to conformational changes in Hsh155's HEAT domain that liberate the first-step reactants for catalysis.
Organizational Affiliation:
Department of Cellular Biochemistry, Max Planck Institute (MPI) for Biophysical Chemistry, Am Fassberg 11, D-37077 Göttingen, Germany.
