Research Article

Molecular architecture of the Saccharomyces cerevisiae activated spliceosome

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Science  25 Aug 2016:
aag1906
DOI: 10.1126/science.aag1906

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Abstract

The activated spliceosome (Bact) 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 S. cerevisiae Bact complex at 5.8 Å resolution. Our model reveals that in Bact 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 Å away from the 5′ss. Our structure suggests that Prp2 ATPase-mediated remodeling leads to conformational changes in Hsh155’s HEAT domain that liberate the first step reactants for catalysis.

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