3E66

Crystal structure of the beta-finger domain of yeast Prp8

Summary for 3E66

• Entry DOI: 10.2210/pdb3e66/pdb
• Descriptor: PRP8 (2 entities in total)
• Functional Keywords: beta-finger, rnase h fold, mrna processing, mrna splicing, nucleus, rna-binding protein, spliceosome, spliceosomal protein, splicing
• Biological source: Saccharomyces cerevisiae
• Cellular location: Nucleus: P33334
• Total number of polymer chains: 2
• Total formula weight: 64374.23

Authors

Yang, K.,Zhang, L.,Xu, T.,Heroux, A.,Zhao, R. (deposition date: 2008-08-14, release date: 2008-10-14, Last modification date: 2024-02-21)

Primary citation

Yang, K.,Zhang, L.,Xu, T.,Heroux, A.,Zhao, R.
Crystal structure of the beta-finger domain of Prp8 reveals analogy to ribosomal proteins.
Proc.Natl.Acad.Sci.Usa, 105:13817-13822, 2008

PubMed 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.

PubMed: 18779563
DOI: 10.1073/pnas.0805960105

Experimental method

X-RAY DIFFRACTION (2.05 Å)