DOI: 10.1126/science.aag1906. Molecular architecture of the <i>Saccharomyces cerevisiae</i> activated spliceosome

Molecular architecture of the Saccharomyces cerevisiae activated spliceosome

10.1126/science.aag1906

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

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.

Bibliography

Rauhut, R., Fabrizio, P., Dybkov, O., Hartmuth, K., Pena, V., Chari, A., Kumar, V., Lee, C.-T., Urlaub, H., Kastner, B., Stark, H., & LÃ¼hrmann, R. (2016). Molecular architecture of the Saccharomyces cerevisiae activated spliceosome. Science, 353(6306), 1399â1405.

Authors 12

Reinhard Rauhut (first)
Patrizia Fabrizio (additional)
Olexandr Dybkov (additional)
Klaus Hartmuth (additional)
Vladimir Pena (additional)
Ashwin Chari (additional)
Vinay Kumar (additional)
Chung-Tien Lee (additional)
Henning Urlaub (additional)
Berthold Kastner (additional)
Holger Stark (additional)
Reinhard Lührmann (additional)

References 74 Referenced 172

Dates

Type	When
Created	8 years, 11 months ago (Aug. 25, 2016, 10:20 p.m.)
Deposited	1 year, 7 months ago (Jan. 15, 2024, 12:21 p.m.)
Indexed	3 months ago (May 18, 2025, 6:22 p.m.)
Issued	8 years, 11 months ago (Sept. 23, 2016)
Published	8 years, 11 months ago (Sept. 23, 2016)
Published Print	8 years, 11 months ago (Sept. 23, 2016)

Funders 1

Deutsche Forschungsgemeinschaft 10.13039/501100001659
Region: Europe
gov (National government)
Labels3
1. German Research Association
2. German Research Foundation
3. DFG
Awards1
1. SFB 860

BibTeX

@article{Rauhut_2016, title={Molecular architecture of the Saccharomyces cerevisiae activated spliceosome}, volume={353}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.aag1906}, DOI={10.1126/science.aag1906}, number={6306}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Rauhut, Reinhard and Fabrizio, Patrizia and Dybkov, Olexandr and Hartmuth, Klaus and Pena, Vladimir and Chari, Ashwin and Kumar, Vinay and Lee, Chung-Tien and Urlaub, Henning and Kastner, Berthold and Stark, Holger and Lührmann, Reinhard}, year={2016}, month=sep, pages={1399–1405} }

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