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Proc Natl Acad Sci U S A. 2008 Sep 16;105(37):13817-22. doi: 10.1073/pnas.0805960105. Epub 2008 Sep 8.

Crystal structure of the beta-finger domain of Prp8 reveals analogy to ribosomal proteins.

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  • 1Department of Biochemistry and Molecular Genetics, Anschutz Medical Campus, University of Colorado Denver, Aurora, CO 80045, USA.

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 beta-hairpin finger protruding out of the protein (hence, this domain will be referred to as the beta-finger domain), resembling many globular ribosomal proteins with protruding extensions. Mutations throughout the beta-finger change the conformational equilibrium between the first and the second catalytic step. Mutations at the base of the beta-finger affect U4/U6 unwinding-mediated spliceosome activation. Prp8 may insert its beta-finger into the first-step complex (U2/U5/U6/pre-mRNA) or U4/U6.U5 tri-snRNP and stabilize these complexes. Mutations on the beta-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.

PMID:
18779563
[PubMed - indexed for MEDLINE]
PMCID:
PMC2544537
Free PMC Article

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