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| | ==Head region of the yeast spliceosomal U4/U6.U5 tri-snRNP== | | ==Head region of the yeast spliceosomal U4/U6.U5 tri-snRNP== |
| - | <StructureSection load='5gao' size='340' side='right' caption='[[5gao]], [[Resolution|resolution]] 3.60Å' scene=''> | + | <SX load='5gao' size='340' side='right' viewer='molstar' caption='[[5gao]], [[Resolution|resolution]] 3.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5gao]] is a 11 chain structure with 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=5GAO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5GAO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5gao]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5GAO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5GAO FirstGlance]. <br> |
| - | </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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.6Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5gao FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gao OCA], [http://pdbe.org/5gao PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5gao RCSB], [http://www.ebi.ac.uk/pdbsum/5gao PDBsum]</span></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=5gao FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gao OCA], [https://pdbe.org/5gao PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5gao RCSB], [https://www.ebi.ac.uk/pdbsum/5gao PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5gao ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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/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/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/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/BRR2_YEAST BRR2_YEAST]] RNA helicase that plays an essential role in pre-mRNA splicing as component of the U5 snRNP and U4/U6-U5 tri-snRNP complexes. Involved in spliceosome assembly, activation and disassembly. Mediates changes in the dynamic network of RNA-RNA interactions in the spliceosome. Catalyzes the ATP-dependent unwinding of U4/U6 RNA duplices, an essential step in the assembly of a catalytically active spliceosome.<ref>PMID:19098916</ref> <ref>PMID:23124065</ref> <ref>PMID:19716790</ref> <ref>PMID:19525970</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/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/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/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> | + | [https://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. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| - | U4/U6.U5 tri-snRNP is a 1.5-megadalton pre-assembled spliceosomal complex comprising U5 small nuclear RNA (snRNA), extensively base-paired U4/U6 snRNAs and more than 30 proteins, including the key components Prp8, Brr2 and Snu114. The tri-snRNP combines with a precursor messenger RNA substrate bound to U1 and U2 small nuclear ribonucleoprotein particles (snRNPs), and transforms into a catalytically active spliceosome after extensive compositional and conformational changes triggered by unwinding of the U4 and U6 (U4/U6) snRNAs. Here we use cryo-electron microscopy single-particle reconstruction of Saccharomyces cerevisiae tri-snRNP at 5.9 A resolution to reveal the essentially complete organization of its RNA and protein components. The single-stranded region of U4 snRNA between its 3' stem-loop and the U4/U6 snRNA stem I is loaded into the Brr2 helicase active site ready for unwinding. Snu114 and the amino-terminal domain of Prp8 position U5 snRNA to insert its loop I, which aligns the exons for splicing, into the Prp8 active site cavity. The structure provides crucial insights into the activation process and the active site of the spliceosome. | + | U4/U6.U5 tri-snRNP represents a substantial part of the spliceosome before activation. A cryo-electron microscopy structure of Saccharomyces cerevisiae U4/U6.U5 tri-snRNP at 3.7 A resolution led to an essentially complete atomic model comprising 30 proteins plus U4/U6 and U5 small nuclear RNAs (snRNAs). The structure reveals striking interweaving interactions of the protein and RNA components, including extended polypeptides penetrating into subunit interfaces. The invariant ACAGAGA sequence of U6 snRNA, which base-pairs with the 5'-splice site during catalytic activation, forms a hairpin stabilized by Dib1 and Prp8 while the adjacent nucleotides interact with the exon binding loop 1 of U5 snRNA. Snu114 harbours GTP, but its putative catalytic histidine is held away from the gamma-phosphate by hydrogen bonding to a tyrosine in the amino-terminal domain of Prp8. Mutation of this histidine to alanine has no detectable effect on yeast growth. The structure provides important new insights into the spliceosome activation process leading to the formation of the catalytic centre. |
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| - | The architecture of the spliceosomal U4/U6.U5 tri-snRNP.,Nguyen TH, Galej WP, Bai XC, Savva CG, Newman AJ, Scheres SH, Nagai K Nature. 2015 Jul 2;523(7558):47-52. doi: 10.1038/nature14548. Epub 2015 Jun 24. PMID:26106855<ref>PMID:26106855</ref>
| + | Cryo-EM structure of the yeast U4/U6.U5 tri-snRNP at 3.7 A resolution.,Nguyen TH, Galej WP, Bai XC, Oubridge C, Newman AJ, Scheres SH, Nagai K Nature. 2016 Feb 18;530(7590):298-302. doi: 10.1038/nature16940. Epub 2016 Feb 1. PMID:26829225<ref>PMID:26829225</ref> |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | <div class="pdbe-citations 5gao" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5gao" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Helicase 3D structures|Helicase 3D structures]] |
| | + | *[[Pre-mRNA splicing factors 3D structures|Pre-mRNA splicing factors 3D structures]] |
| | + | *[[Sm-like protein|Sm-like protein]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| - | </StructureSection> | + | </SX> |
| - | [[Category: RNA helicase]] | + | [[Category: Large Structures]] |
| | [[Category: Saccharomyces cerevisiae]] | | [[Category: Saccharomyces cerevisiae]] |
| - | [[Category: Bai, X C]] | + | [[Category: Bai XC]] |
| - | [[Category: Galej, W P]] | + | [[Category: Galej WP]] |
| - | [[Category: Nagai, K]] | + | [[Category: Nagai K]] |
| - | [[Category: Newman, A J]] | + | [[Category: Newman AJ]] |
| - | [[Category: Nguyen, T H.D]] | + | [[Category: Nguyen THD]] |
| - | [[Category: Oubridge, C]] | + | [[Category: Oubridge C]] |
| - | [[Category: Scheres, S H.W]] | + | [[Category: Scheres SHW]] |
| - | [[Category: Gtpase]]
| + | |
| - | [[Category: Pre-mrna splicing]]
| + | |
| - | [[Category: Snrnp]]
| + | |
| - | [[Category: Spliceosome]]
| + | |
| - | [[Category: Transcription]]
| + | |
