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2p8r

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[[Image:2p8r.gif|left|200px]]<br /><applet load="2p8r" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="2p8r, resolution 2.100&Aring;" />
 
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'''Crystal structure of the C-terminal domain of C. elegans pre-mRNA splicing factor Prp8 carrying R2303K mutant'''<br />
 
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==Overview==
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==Crystal structure of the C-terminal domain of C. elegans pre-mRNA splicing factor Prp8 carrying R2303K mutant==
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Prp8 is a critical pre-mRNA splicing factor. Prp8 is proposed to help form and stabilize the spliceosome catalytic core and to be an important regulator of spliceosome activation. Mutations in human Prp8 (hPrp8) cause a severe form of the genetic disorder retinitis pigmentosa, RP13. Understanding the molecular mechanism of Prp8's function in pre-mRNA splicing and RP13 has been hindered by its large size (over 2000 amino acids) and remarkably low-sequence similarity with other proteins. Here we present the crystal structure of the C-terminal domain (the last 273 residues) of Caenorhabditis elegans Prp8 (cPrp8). The core of the C-terminal domain is an alpha/beta structure that forms the MPN (Mpr1, Pad1 N-terminal) fold but without Zn(2+) coordination. We propose that the C-terminal domain is a protein interaction domain instead of a Zn(2+)-dependent metalloenzyme as proposed for some MPN proteins. Mapping of RP13 mutants on the Prp8 structure suggests that these residues constitute a binding surface between Prp8 and other partner(s), and the disruption of this interaction provides a plausible molecular mechanism for RP13.
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<StructureSection load='2p8r' size='340' side='right'caption='[[2p8r]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2p8r]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Caenorhabditis_elegans Caenorhabditis elegans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P8R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2P8R FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2p8r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p8r OCA], [https://pdbe.org/2p8r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2p8r RCSB], [https://www.ebi.ac.uk/pdbsum/2p8r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2p8r ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/PRP8_CAEEL PRP8_CAEEL] Functions as a scaffold that mediates the ordered assembly of spliceosomal proteins and snRNAs. Required for the assembly of the U4/U6-U5 tri-snRNP complex. Functions as scaffold that positions spliceosomal U2, U5 and U6 snRNAs at splice sites on pre-mRNA substrates, so that splicing can occur. Interacts with both the 5' and the 3' splice site (By similarity).
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/p8/2p8r_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2p8r ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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2P8R is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Caenorhabditis_elegans Caenorhabditis elegans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P8R OCA].
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*[[Pre-mRNA splicing factors 3D structures|Pre-mRNA splicing factors 3D structures]]
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__TOC__
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==Reference==
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</StructureSection>
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Crystal structure of the C-terminal domain of splicing factor Prp8 carrying retinitis pigmentosa mutants., Zhang L, Shen J, Guarnieri MT, Heroux A, Yang K, Zhao R, Protein Sci. 2007 Jun;16(6):1024-31. Epub 2007 May 1. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17473007 17473007]
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[[Category: Caenorhabditis elegans]]
[[Category: Caenorhabditis elegans]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Guarnieri, M T.]]
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[[Category: Guarnieri MT]]
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[[Category: Heroux, A.]]
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[[Category: Heroux A]]
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[[Category: Shen, J.]]
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[[Category: Shen J]]
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[[Category: Yang, K.]]
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[[Category: Yang K]]
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[[Category: Zhang, L.]]
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[[Category: Zhang L]]
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[[Category: Zhao, R.]]
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[[Category: Zhao R]]
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[[Category: alpha-beta]]
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[[Category: splicing]]
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[[Category: translation]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:27:04 2008''
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Current revision

Crystal structure of the C-terminal domain of C. elegans pre-mRNA splicing factor Prp8 carrying R2303K mutant

PDB ID 2p8r

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