In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 105, No. 37 ( 2008-09-16), p. 13817-13822
Abstract:
Prp8 stands out among hundreds of splicing factors as a key regulator of spliceosome activation and a potential cofactor of the splicing reaction. We present here the crystal structure of a 274-residue domain (residues 1,822–2,095) near the C terminus of Saccharomyces cerevisiae Prp8. The most striking feature of this domain is a β-hairpin finger protruding out of the protein (hence, this domain will be referred to as the β-finger domain), resembling many globular ribosomal proteins with protruding extensions. Mutations throughout the β-finger change the conformational equilibrium between the first and the second catalytic step. Mutations at the base of the β-finger affect U4/U6 unwinding-mediated spliceosome activation. Prp8 may insert its β-finger into the first-step complex (U2/U5/U6/pre-mRNA) or U4/U6.U5 tri-snRNP and stabilize these complexes. Mutations on the β-finger likely alter these interactions, leading to the observed mutant phenotypes. Our results suggest a possible mechanism of how Prp8 regulates spliceosome activation. These results also demonstrate an analogy between a spliceosomal protein and ribosomal proteins that insert extensions into folded rRNAs and stabilize the ribosome.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.0805960105
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2008
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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