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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2007-2-23
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pubmed:abstractText |
Protein Prp8 interacts with several other spliceosomal proteins, snRNAs, and the pre-mRNA and thereby organizes the active site(s) of the spliceosome. The DEAD-box protein Brr2 and the GTPase Snu114 bind to the Prp8 C terminus, a region where mutations in human Prp8 are linked to the RP13 form of Retinitis pigmentosa. We show crystallographically that the C-terminal domain of yeast Prp8p exhibits a Jab1/MPN-like core known from deubiquitinating enzymes. Insertions and terminal appendices are grafted onto this core, covering a putative isopeptidase center whose metal binding site is additionally impaired. Targeted yeast-two-hybrid analyses show that the RP13-linked region in the C-terminal appendix of human Prp8 is essential for binding of human Brr2 and Snu114, and that RP13 point mutations in this fragment weaken these interactions. We conclude that the expanded Prp8 Jab1/MPN domain represents a pseudoenzyme converted into a protein-protein interaction platform and that dysfunction of this platform underlies Retinitis pigmentosa.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/BRR2 protein, S cerevisiae,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Mutant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PRP8 protein, S cerevisiae,
http://linkedlifedata.com/resource/pubmed/chemical/PRPF8 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/RNA Helicases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ribonucleoprotein, U4-U6 Small...,
http://linkedlifedata.com/resource/pubmed/chemical/Ribonucleoprotein, U5 Small Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/SNU114 protein, S cerevisiae,
http://linkedlifedata.com/resource/pubmed/chemical/Saccharomyces cerevisiae Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1097-2765
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
23
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pubmed:volume |
25
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
615-24
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17317632-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:17317632-Amino Acid Motifs,
pubmed-meshheading:17317632-Amino Acid Sequence,
pubmed-meshheading:17317632-Binding Sites,
pubmed-meshheading:17317632-Carrier Proteins,
pubmed-meshheading:17317632-Crystallography, X-Ray,
pubmed-meshheading:17317632-Humans,
pubmed-meshheading:17317632-Models, Molecular,
pubmed-meshheading:17317632-Molecular Sequence Data,
pubmed-meshheading:17317632-Mutant Proteins,
pubmed-meshheading:17317632-Mutation,
pubmed-meshheading:17317632-Peptide Fragments,
pubmed-meshheading:17317632-Protein Binding,
pubmed-meshheading:17317632-Protein Folding,
pubmed-meshheading:17317632-Protein Structure, Tertiary,
pubmed-meshheading:17317632-RNA Helicases,
pubmed-meshheading:17317632-RNA-Binding Proteins,
pubmed-meshheading:17317632-Repressor Proteins,
pubmed-meshheading:17317632-Retinitis Pigmentosa,
pubmed-meshheading:17317632-Ribonucleoprotein, U4-U6 Small Nuclear,
pubmed-meshheading:17317632-Ribonucleoprotein, U5 Small Nuclear,
pubmed-meshheading:17317632-Saccharomyces cerevisiae Proteins,
pubmed-meshheading:17317632-Sequence Alignment,
pubmed-meshheading:17317632-Ubiquitin
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pubmed:year |
2007
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pubmed:articleTitle |
Structure of a multipartite protein-protein interaction domain in splicing factor prp8 and its link to retinitis pigmentosa.
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pubmed:affiliation |
AG Röntgenkristallographie, Max-Planck-Institut für Biophysikalische Chemie, Am Fassberg 11, D-37077 Göttingen, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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