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| | <SX load='5mps' size='340' side='right' viewer='molstar' caption='[[5mps]], [[Resolution|resolution]] 3.85Å' scene=''> | | <SX load='5mps' size='340' side='right' viewer='molstar' caption='[[5mps]], [[Resolution|resolution]] 3.85Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5mps]] is a 30 chain structure with sequence from [http://en.wikipedia.org/wiki/ ], [http://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824] and [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MPS OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5MPS FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5mps]] 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=5MPS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MPS 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=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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]] 3.85Å</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='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=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UBC4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 ATCC 18824])</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=5mps FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mps OCA], [https://pdbe.org/5mps PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mps RCSB], [https://www.ebi.ac.uk/pdbsum/5mps PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mps ProSAT]</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=5mps FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mps OCA], [http://pdbe.org/5mps PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mps RCSB], [http://www.ebi.ac.uk/pdbsum/5mps PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mps ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/BUD31_YEAST BUD31_YEAST]] Involved in pre-mRNA splicing. Important for bud site selection. [[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/SN114_YEAST SN114_YEAST]] Component of the U5 snRNP complex required for pre-mRNA splicing. Binds GTP. [[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/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/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/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/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/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/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/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/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/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/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/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/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/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/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/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/CWC15_YEAST CWC15_YEAST]] Involved in pre-mRNA splicing. [[http://www.uniprot.org/uniprot/CWC22_YEAST CWC22_YEAST]] May be involved in pre-mRNA splicing. [[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/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/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> | + | [https://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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 23: |
Line 22: |
| | ==See Also== | | ==See Also== |
| | *[[Pre-mRNA splicing factors 3D structures|Pre-mRNA splicing factors 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__ |
| | </SX> | | </SX> |
| - | [[Category: Atcc 18824]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: Saccharomyces cerevisiae]] | | [[Category: Saccharomyces cerevisiae]] |
| - | [[Category: Bai, X C]] | + | [[Category: Bai X-C]] |
| - | [[Category: Fica, S M]] | + | [[Category: Fica SM]] |
| - | [[Category: Galej, W P]] | + | [[Category: Galej WP]] |
| - | [[Category: Nagai, K]] | + | [[Category: Nagai K]] |
| - | [[Category: Newman, A J]] | + | [[Category: Newman AJ]] |
| - | [[Category: Oubridge, C]] | + | [[Category: Oubridge C]] |
| - | [[Category: Wilkinson, M E]] | + | [[Category: Wilkinson ME]] |
| - | [[Category: Complex c-star]]
| + | |
| - | [[Category: Lariat intermediate]]
| + | |
| - | [[Category: Pre-mrna splicing]]
| + | |
| - | [[Category: Splicing]]
| + | |
| - | [[Category: Trans-esterification]]
| + | |
| Structural highlights
Function
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).[1] [2] [3] [4] [5]
Publication Abstract from PubMed
The spliceosome excises introns from pre-mRNAs in two sequential trans-esterifications - branching and exon ligation1 - catalysed at a single catalytic metal site in U6 snRNA2,3. The recent structures of the spliceosomal C complex4,5 with the cleaved 5'-exon and lariat-3'-exon bound to the catalytic centre revealed that branching-specific factors such as Cwc25 lock the branch helix into position for nucleophilic attack of the branch adenosine at the 5'-splice site. Furthermore, the ATPase Prp16 is positioned to bind and translocate the intron downstream of the branch point to destabilize branching-specific factors and release the branch helix from the active site4. Here we present the 3.8 A cryo-electron microscopy structure of a Saccharomyces cerevisiae spliceosome stalled after Prp16-mediated remodelling but prior to exon ligation. While the U6 snRNA catalytic core remains firmly held in the active site cavity of Prp8 by proteins common to both steps, the branch helix has rotated by 75 degrees compared to complex C and is stabilized into a new position by Prp17, Cef1, and the reoriented Prp8 RNaseH domain. This rotation of the branch helix removes the branch adenosine from the catalytic core, creates a space for 3'-exon docking, and restructures the pairing of the 5'-splice site with the U6 snRNA ACAGAGA region. Slu7 and Prp18, which promote exon ligation, bind together to the Prp8 RNaseH domain. The ATPase Prp22, bound to Prp8 in place of Prp16, could interact with the 3'-exon, suggesting a possible basis for mRNA release after exon ligation6,7. Together with the C complex structure4, our new C* complex structure reveals the two major conformations of the spliceosome during the catalytic stages of splicing.
Structure of a spliceosome remodelled for exon ligation.,Fica SM, Oubridge C, Galej WP, Wilkinson ME, Bai XC, Newman AJ, Nagai K Nature. 2017 Jan 11. doi: 10.1038/nature21078. PMID:28076345[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Chung S, McLean MR, Rymond BC. Yeast ortholog of the Drosophila crooked neck protein promotes spliceosome assembly through stable U4/U6.U5 snRNP addition. RNA. 1999 Aug;5(8):1042-54. PMID:10445879
- ↑ Ben-Yehuda S, Dix I, Russell CS, McGarvey M, Beggs JD, Kupiec M. Genetic and physical interactions between factors involved in both cell cycle progression and pre-mRNA splicing in Saccharomyces cerevisiae. Genetics. 2000 Dec;156(4):1503-17. PMID:11102353
- ↑ Russell CS, Ben-Yehuda S, Dix I, Kupiec M, Beggs JD. Functional analyses of interacting factors involved in both pre-mRNA splicing and cell cycle progression in Saccharomyces cerevisiae. RNA. 2000 Nov;6(11):1565-72. PMID:11105756
- ↑ Zhu W, Rainville IR, Ding M, Bolus M, Heintz NH, Pederson DS. Evidence that the pre-mRNA splicing factor Clf1p plays a role in DNA replication in Saccharomyces cerevisiae. Genetics. 2002 Apr;160(4):1319-33. PMID:11973290
- ↑ Wang Q, Hobbs K, Lynn B, Rymond BC. The Clf1p splicing factor promotes spliceosome assembly through N-terminal tetratricopeptide repeat contacts. J Biol Chem. 2003 Mar 7;278(10):7875-83. Epub 2002 Dec 31. PMID:12509417 doi:http://dx.doi.org/10.1074/jbc.M210839200
- ↑ Fica SM, Oubridge C, Galej WP, Wilkinson ME, Bai XC, Newman AJ, Nagai K. Structure of a spliceosome remodelled for exon ligation. Nature. 2017 Jan 11. doi: 10.1038/nature21078. PMID:28076345 doi:http://dx.doi.org/10.1038/nature21078
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