2og4: Difference between revisions

Revision as of 19:18, 21 February 2008

Structure of an expanded Jab1-MPN-like domain of splicing factor Prp8p from yeast

OverviewOverview

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.

About this StructureAbout this Structure

2OG4 is a Single protein structure of sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA.

ReferenceReference

Structure of a multipartite protein-protein interaction domain in splicing factor prp8 and its link to retinitis pigmentosa., Pena V, Liu S, Bujnicki JM, Luhrmann R, Wahl MC, Mol Cell. 2007 Feb 23;25(4):615-24. PMID:17317632

Page seeded by OCA on Thu Feb 21 18:18:05 2008

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OCA

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-[[Image:2og4.gif|left|200px]]<br /><applet load="2og4" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:2og4.gif|left|200px]]<br /><applet load="2og4" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="2og4, resolution 2.00&Aring;" />
 '''Structure of an expanded Jab1-MPN-like domain of splicing factor Prp8p from yeast'''<br />
 ==Overview==
-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.
+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.
 ==About this Structure==
-OG4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2OG4 OCA].
+OG4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OG4 OCA].
 ==Reference==
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 [[Category: Luehrmann, R.]]
 [[Category: Pena, V.]]
-[[Category: Wahl, M.C.]]
+[[Category: Wahl, M C.]]
 [[Category: isopeptidase]]
 [[Category: jab1/mpn domain]]
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 [[Category: x-ray crystallography]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 13:09:56 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:18:05 2008''