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==Open and closed forms of V1788D human PRP8 RNase H-like domain with bound Mg ion==
<StructureSection load='4jkb' size='340' side='right'caption='[[4jkb]], [[Resolution|resolution]] 1.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4jkb]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JKB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JKB FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4jkb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jkb OCA], [https://pdbe.org/4jkb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jkb RCSB], [https://www.ebi.ac.uk/pdbsum/4jkb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jkb ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/PRP8_HUMAN PRP8_HUMAN] Defects in PRPF8 are the cause of retinitis pigmentosa type 13 (RP13) [MIM:[https://omim.org/entry/600059 600059]. RP leads to degeneration of retinal photoreceptor cells. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP13 inheritance is autosomal dominant.<ref>PMID:17317632</ref> <ref>PMID:11468273</ref> [:]<ref>PMID:11910553</ref> <ref>PMID:12714658</ref> 
== Function ==
[https://www.uniprot.org/uniprot/PRP8_HUMAN PRP8_HUMAN] Central component of the spliceosome, which may play a role in aligning the pre-mRNA 5'- and 3'-exons for ligation. Interacts with U5 snRNA, and with pre-mRNA 5'-splice sites in B spliceosomes and 3'-splice sites in C spliceosomes.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Splicing of pre-mRNAs in eukaryotes is catalyzed by the spliceosome, a large RNA-protein metalloenzyme. The catalytic center of the spliceosome involves a structure comprising the U2 and U6 snRNAs and includes a metal bound by U6 snRNA. The precise architecture of the splicesome active site, however, and the question of whether it includes protein components, remains unresolved. A wealth of evidence places the protein PRP8 at the heart of the spliceosome through assembly and catalysis. Here we provide evidence that the RNase H domain of PRP8 undergoes a conformational switch between the two steps of splicing, rationalizing yeast prp8 alleles that promote either the first or second step. We also show that this switch unmasks a metal-binding site involved in the second step. Together, these data establish that PRP8 is a metalloprotein that promotes exon ligation within the spliceosome.

A conformational switch in PRP8 mediates metal ion coordination that promotes pre-mRNA exon ligation.,Schellenberg MJ, Wu T, Ritchie DB, Fica S, Staley JP, Atta KA, Lapointe P, Macmillan AM Nat Struct Mol Biol. 2013 May 19. doi: 10.1038/nsmb.2556. PMID:23686287<ref>PMID:23686287</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4jkb" style="background-color:#fffaf0;"></div>

==See Also==
*[[Pre-mRNA splicing factors 3D structures|Pre-mRNA splicing factors 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Atta KA]]
[[Category: MacMillan AM]]
[[Category: Ritchie DB]]
[[Category: Schellenberg MJ]]
[[Category: Wu T]]