View source for 6exn


==Post-catalytic P complex spliceosome with 3' splice site docked==
<SX load='6exn' size='340' side='right' viewer='molstar' caption='[[6exn]], [[Resolution|resolution]] 3.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6exn]] is a 46 chain structure with sequence from [http://en.wikipedia.org/wiki/ ], [http://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast], [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] and [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_s288c Saccharomyces cerevisiae s288c]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EXN OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6EXN FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=IHP:INOSITOL+HEXAKISPHOSPHATE'>IHP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5mq0|5mq0]], [[5wsg|5wsg]], [[5xjc|5xjc]], [[5mqf|5mqf]]</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA_helicase RNA helicase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.4.13 3.6.4.13] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6exn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6exn OCA], [http://pdbe.org/6exn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6exn RCSB], [http://www.ebi.ac.uk/pdbsum/6exn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6exn ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/PRP17_YEAST PRP17_YEAST]] May function in the second step of pre-mRNA splicing. Regulatory protein involved in replication and mitotic spindle formation and/or maintenance. Required for initiation and completion of S-phase and for initiation and completion of DNA replication. Might be required for the maintenance of microtubules. Essential only at elevated temperatures. [[http://www.uniprot.org/uniprot/SMD2_YEAST SMD2_YEAST]] Involved in pre-mRNA splicing. Binds snRNA U1, U2, U4 and U5 which contain a highly conserved structural motif called the Sm binding site. [[http://www.uniprot.org/uniprot/RU2A_YEAST RU2A_YEAST]] Involved in pre-mRNA splicing. Associates to U2 snRNA in a MSL1 dependent manner and is required for normal accumulation of U2 snRNA. Required for the spliceosome assembly and the efficient addition of U2 snRNP onto the pre-mRNA.<ref>PMID:9799242</ref>  [[http://www.uniprot.org/uniprot/SLU7_YEAST SLU7_YEAST]] Essential protein involved in the second catalytic step of pre-mRNA splicing. Involved in the selection of 3'-type splice sites; this selection could be done via a 3'-splice site-binding factor, PRP16.<ref>PMID:11158289</ref> <ref>PMID:12212850</ref> <ref>PMID:1406691</ref> <ref>PMID:1427075</ref> <ref>PMID:7568198</ref> <ref>PMID:7664739</ref> <ref>PMID:8756413</ref> <ref>PMID:9153314</ref> <ref>PMID:9528778</ref>  [[http://www.uniprot.org/uniprot/CWC21_YEAST CWC21_YEAST]] Involved in pre-mRNA splicing. May function at or prior to the first catalytic step of splicing at the catalytic center of the spliceosome, together with ISY1. May do so by stabilizing the catalytic center or the position of the RNA substrate.<ref>PMID:19789211</ref> <ref>PMID:19854871</ref>  [[http://www.uniprot.org/uniprot/CLF1_YEAST CLF1_YEAST]] Involved in pre-mRNA splicing and cell cycle progression. Required for the spliceosome assembly by promoting the functional integration of the U4/U6.U5 tri-snRNP particle into the U1-, U2-dependent pre-spliceosome. Also recruits PRP19 to the spliceosome, as a component of the NTC complex (or PRP19-associated complex). The association of the NTC complex to the spliceosome mediates conformational rearrangement or stabilizes the structure of the spliceosome after U4 snRNA dissociation, which leads to spliceosome maturation. Required for initiation of the DNA replication by binding the RNA replication origins, probably through its interaction with the origin recognition complex (ORC).<ref>PMID:10445879</ref> <ref>PMID:11102353</ref> <ref>PMID:11105756</ref> <ref>PMID:11973290</ref> <ref>PMID:12509417</ref>  [[http://www.uniprot.org/uniprot/RUXG_YEAST RUXG_YEAST]] Involved in pre-mRNA splicing. Binds snRNA U1, U2, U4 and U5 which contain a highly conserved structural motif called the Sm binding site. [[http://www.uniprot.org/uniprot/CWC15_YEAST CWC15_YEAST]] Involved in pre-mRNA splicing. [[http://www.uniprot.org/uniprot/SMD3_YEAST SMD3_YEAST]] Involved in pre-mRNA splicing. Binds snRNA U1, U2, U4 and U5 which contain a highly conserved structural motif called the Sm binding site. Also binds telomerase RNA and is required for its accumulation.<ref>PMID:10490028</ref> <ref>PMID:7799953</ref>  [[http://www.uniprot.org/uniprot/RSMB_YEAST RSMB_YEAST]] Involved in pre-mRNA splicing. Binds snRNA U1, U2, U4 and U5 which contain a highly conserved structural motif called the Sm binding site. [[http://www.uniprot.org/uniprot/RUXE_YEAST RUXE_YEAST]] Involved in pre-mRNA splicing. Binds and is required for the stability of snRNA U1, U2, U4 and U5 which contain a highly conserved structural motif called the Sm binding site. Involved in cap modification.<ref>PMID:8918241</ref>  [[http://www.uniprot.org/uniprot/PRP22_YEAST PRP22_YEAST]] Acts late in the splicing of pre-mRNA. Mediates the release of the spliced mRNA from spliceosomes. [[http://www.uniprot.org/uniprot/SLT11_YEAST SLT11_YEAST]] Involved in pre-mRNA splicing. Facilitates the cooperative formation of U2/U6 helix II in association with stem II in the spliceosome. Binds to RNA.<ref>PMID:11158289</ref> <ref>PMID:9528778</ref>  [[http://www.uniprot.org/uniprot/PRP18_YEAST PRP18_YEAST]] Component of the U4/U5/U6 snRNP, binding principally to the u5 snRNP. It is not absolutely required for the second step of pre-mRNA splicing at low temperatures but is required at higher temperatures. It may stabilize a particular conformation of the U5 snRNP or orient the U5 snRNP within the U4/U5/U6 snRNP or within the spliceosome. [[http://www.uniprot.org/uniprot/PRP46_YEAST PRP46_YEAST]] Involved in pre-mRNA splicing. May also be required for cell cycle progression at G2/M (By similarity).<ref>PMID:12554883</ref>  [[http://www.uniprot.org/uniprot/SMD1_YEAST SMD1_YEAST]] Involved in pre-mRNA splicing. Binds snRNA U1, U2, U4 and U5 which contain a highly conserved structural motif called the Sm binding site. Also binds telomerase RNA and is required for its accumulation.<ref>PMID:10490028</ref> <ref>PMID:8430095</ref>  [[http://www.uniprot.org/uniprot/PRP19_YEAST PRP19_YEAST]] Involved in pre-mRNA splicing. Acts a central component of the NTC complex (or PRP19-associated complex) that associates to the spliceosome to mediate conformational rearrangement or to stabilize the structure of the spliceosome after U4 snRNA dissociation, which leads to spliceosome maturation. Involved in DNA repair. [[http://www.uniprot.org/uniprot/PRP45_YEAST PRP45_YEAST]] Involved in pre-mRNA splicing. Associated with the spliceosome throughout the splicing reactions, until after the second catalytic step.<ref>PMID:12359070</ref> <ref>PMID:12554883</ref>  [[http://www.uniprot.org/uniprot/CWC2_YEAST CWC2_YEAST]] Involved in the first step of pre-mRNA splicing. Required for cell growth and cell cycle control. Plays a role in the levels of the U1, U4, U5 and U6 snRNAs and the maintenance of the U4/U6 snRNA complex. May provide the link between the "nineteen complex" NTC spliceosome protein complex and the spliceosome through the U6 snRNA. Associates predominantly with U6 snRNAs in assembled active spliceosomes. Binds directly to the internal stem-loop (ISL) domain of the U6 snRNA and to the pre-mRNA intron near the 5' splice site during the activation and catalytic phases of the spliceosome cycle. Binds also to U1, U4, U5 and U6 snRNAs and to pre-mRNAs, in vitro. Is not required for the Prp2-mediated remodeling of the activated spliceosome.<ref>PMID:19435883</ref> <ref>PMID:22246180</ref>  [[http://www.uniprot.org/uniprot/MSL1_YEAST MSL1_YEAST]] Involved in pre-mRNA splicing. This protein is associated with snRNP U2. It binds stem loop IV of U2 snRNA.<ref>PMID:8649387</ref>  [[http://www.uniprot.org/uniprot/RUXF_YEAST RUXF_YEAST]] Involved in pre-mRNA splicing. Binds snRNA U1, U2, U4 and U5 which contain a highly conserved structural motif called the Sm binding site. [[http://www.uniprot.org/uniprot/SYF2_YEAST SYF2_YEAST]] Involved in pre-mRNA splicing and cell cycle control. As a component of the NTC complex (or PRP19-associated complex), associates to the spliceosome to mediate conformational rearrangement or to stabilize the structure of the spliceosome after U4 snRNA dissociation, which leads to spliceosome maturation. The cell cycle arrest of SYF2 defective cells may be due to the inefficient splicing of TUB1.<ref>PMID:11102353</ref> <ref>PMID:11105756</ref> <ref>PMID:12384582</ref>  [[http://www.uniprot.org/uniprot/BUD31_YEAST BUD31_YEAST]] Involved in pre-mRNA splicing. Important for bud site selection. [[http://www.uniprot.org/uniprot/CEF1_YEAST CEF1_YEAST]] Involved in pre-mRNA splicing and cell cycle control. Required for the binding of the NTC complex (or PRP19-associated complex) components to the spliceosome to mediate conformational rearrangement or to stabilize the structure of the spliceosome after U4 snRNA dissociation, which leads to spliceosome maturation. Its absence leads to an arrest of the cell cycle, possibly due to the inefficient splicing of TUB1.<ref>PMID:10092627</ref> <ref>PMID:10570151</ref> <ref>PMID:11784857</ref> <ref>PMID:9632794</ref>  [[http://www.uniprot.org/uniprot/CWC22_YEAST CWC22_YEAST]] May be involved in pre-mRNA splicing. [[http://www.uniprot.org/uniprot/PRP8_YEAST PRP8_YEAST]] Required for pre-spliceosome formation, which is the first step of pre-mRNA splicing. This protein is associated with snRNP U5. Has a role in branch site-3' splice site selection. Associates with the branch site-3' splice 3'-exon region. Also has a role in cell cycle.<ref>PMID:2835658</ref> <ref>PMID:9150140</ref> <ref>PMID:12773561</ref> <ref>PMID:18779563</ref>  [[http://www.uniprot.org/uniprot/SN309_YEAST SN309_YEAST]] Involved in pre-mRNA splicing by stabilizing the NTC (or PRP19-associated complex). As a component of the NTC complex, associates to the spliceosome to mediate conformational rearrangement or to stabilize the structure of the spliceosome after U4 snRNA dissociation, which leads to spliceosome maturation.<ref>PMID:10318896</ref> <ref>PMID:9528791</ref>  [[http://www.uniprot.org/uniprot/SYF1_YEAST SYF1_YEAST]] Involved in pre-mRNA splicing and cell cycle control. As a component of the NTC complex (or PRP19-associated complex), associates to the spliceosome to mediate conformational rearrangement or to stabilize the structure of the spliceosome after U4 snRNA dissociation, which leads to spliceosome maturation.<ref>PMID:11102353</ref> <ref>PMID:11105756</ref>  [[http://www.uniprot.org/uniprot/SN114_YEAST SN114_YEAST]] Component of the U5 snRNP complex required for pre-mRNA splicing. Binds GTP. 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Introns are removed from eukaryotic messenger RNA precursors by the spliceosome in two transesterification reactions-branching and exon ligation. The mechanism of 3'-splice site recognition during exon ligation has remained unclear. Here we present the 3.7-angstrom cryo-electron microscopy structure of the yeast P-complex spliceosome immediately after exon ligation. The 3'-splice site AG dinucleotide is recognized through non-Watson-Crick pairing with the 5' splice site and the branch-point adenosine. After the branching reaction, protein factors work together to remodel the spliceosome and stabilize a conformation competent for 3'-splice site docking, thereby promoting exon ligation. The structure accounts for the strict conservation of the GU and AG dinucleotides at the 5' and 3' ends of introns and provides insight into the catalytic mechanism of exon ligation.

Postcatalytic spliceosome structure reveals mechanism of 3'-splice site selection.,Wilkinson ME, Fica SM, Galej WP, Norman CM, Newman AJ, Nagai K Science. 2017 Dec 8;358(6368):1283-1288. doi: 10.1126/science.aar3729. Epub 2017 , Nov 16. PMID:29146871<ref>PMID:29146871</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6exn" style="background-color:#fffaf0;"></div>

==See Also==
*[[Nucleoprotein 3D structures|Nucleoprotein 3D structures]]
*[[Pre-mRNA splicing factors 3D structures|Pre-mRNA splicing factors 3D structures]]
== References ==
<references/>
__TOC__
</SX>
[[Category: Baker's yeast]]
[[Category: Large Structures]]
[[Category: RNA helicase]]
[[Category: Saccharomyces cerevisiae]]
[[Category: Saccharomyces cerevisiae s288c]]
[[Category: Fica, S M]]
[[Category: Galej, W P]]
[[Category: Nagai, K]]
[[Category: Newman, A J]]
[[Category: Norman, C M]]
[[Category: Wilkinson, M E]]
[[Category: Exon ligation]]
[[Category: P-complex]]
[[Category: Spliceosome]]
[[Category: Splicing]]