View source for 5zwm


==Cryo-EM structure of the yeast pre-B complex at an average resolution of 3.4~4.6 angstrom (tri-snRNP and U2 snRNP Part)==
<SX load='5zwm' size='340' side='right' viewer='molstar' caption='[[5zwm]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5zwm]] is a 57 chain structure with sequence from [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=5ZWM OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5ZWM 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=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5zwn|5zwn]], [[5zwo|5zwo]]</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=5zwm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zwm OCA], [http://pdbe.org/5zwm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zwm RCSB], [http://www.ebi.ac.uk/pdbsum/5zwm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zwm ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/CUS1_YEAST CUS1_YEAST]] Essential splicing protein required for U2 snRNP binding to pre-mRNA during spliceosome assembly. [[http://www.uniprot.org/uniprot/SF3B1_YEAST SF3B1_YEAST]] Contacts pre-mRNA on both sides of the branch site early in spliceosome assembly. [[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/SNU13_YEAST SNU13_YEAST]] Common component of the spliceosome and rRNA processing machinery. In association with the spliceosomal U4/U6.U5 tri-snRNP particle, required for splicing of pre-mRNA. In association with box C/D snoRNPs, required for processing of pre-ribosomal RNA (rRNA) and site-specific 2'-O-methylation of substrate RNAs. Essential for the accumulation and stability of U4 snRNA, U6 snRNA, and box C/D snoRNAs.<ref>PMID:11081632</ref> <ref>PMID:12215523</ref> <ref>PMID:14730029</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/PRP4_YEAST PRP4_YEAST]] Involved in RNA splicing. Is required for the association of U4/U6 snRNP with U5 snRNP in an early step of spliceosome assembly. [[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/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/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/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/PML1_YEAST PML1_YEAST]] Required for efficient splicing and pre-mRNA nuclear retention.<ref>PMID:15565172</ref>  [[http://www.uniprot.org/uniprot/LSM7_YEAST LSM7_YEAST]] Component of LSm protein complexes, which are involved in RNA processing and may function in a chaperone-like manner. Component of the cytoplasmic LSM1-LSM7 complex which is thought to be involved in mRNA degradation by activating the decapping step. Component of the nuclear LSM2-LSM8 complex, which is involved in splicing of nuclear mRNAs. LSM2-LSM8 associates with multiple snRNP complexes containing the U6 snRNA (U4/U6 snRNP, spliceosomal U4/U6.U5 snRNP, and free U6 snRNP). It binds directly to the U6 snRNA and plays a role in the biogenesis and stability of the U6 snRNP and U4/U6 snRNP complexes. It probably also is involved degradation of nuclear pre-mRNA by targeting them for decapping. LSM7 binds specifically to the 3'-terminal U-tract of U6 snRNA. LSM2-LSM8 probably is involved in processing of pre-tRNAs, pre-rRNAs and U3 snoRNA. LSM7, probably in a complex that contains LSM2-LSM7 but not LSM1 or LSM8, associates with the precursor of the RNA component of RNase P (pre-P RNA) and may be involved in maturing pre-P RNA.<ref>PMID:10747033</ref> <ref>PMID:10761922</ref> <ref>PMID:15485930</ref>  [[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>  [[http://www.uniprot.org/uniprot/LSM2_YEAST LSM2_YEAST]] Component of LSm protein complexes, which are involved in RNA processing and may function in a chaperone-like manner. Component of the cytoplasmic LSM1-LSM7 complex which is thought to be involved in mRNA degradation by activating the decapping step. Component of the nuclear LSM2-LSM8 complex, which is involved in splicing of nuclear mRNAs. LSM2-LSM8 associates with multiple snRNP complexes containing the U6 snRNA (U4/U6 snRNP, U4/U6.U5 snRNP, and free U6 snRNP). It binds directly to the U6 snRNA and plays a role in the biogenesis and stability of the U6 snRNP and U4/U6 snRNP complexes. It probably also is involved degradation of nuclear pre-mRNA by targeting them for decapping. LSM2 binds specifically to the 3'-terminal U-tract of U6 snRNA. LSM2-LSM8 probably is involved in processing of pre-tRNAs, pre-rRNAs and U3 snoRNA. LSM2, probably in a complex that contains LSM2-LSM7 but not LSM1 or LSM8, associates with the precursor of the RNA component of RNase P (pre-P RNA) and may be involved in maturing pre-P RNA. LSM2 is required for processing of pre-tRNAs, pre-rRNAs and U3 snoRNA.<ref>PMID:10747033</ref> <ref>PMID:12077351</ref> <ref>PMID:12438310</ref> <ref>PMID:14627812</ref> <ref>PMID:15485930</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/HSH49_YEAST HSH49_YEAST]] Possible SF3b-like factor. [[http://www.uniprot.org/uniprot/LSM3_YEAST LSM3_YEAST]] Component of LSm protein complexes, which are involved in RNA processing and may function in a chaperone-like manner. Component of the cytoplasmic LSM1-LSM7 complex which is thought to be involved in mRNA degradation by activating the decapping step. Component of the nuclear LSM2-LSM8 complex, which is involved in splicing of nuclear mRNAs. LSM2-LSM8 associates with multiple snRNP complexes containing the U6 snRNA (U4/U6 snRNP, U4/U6.U5 snRNP, and free U6 snRNP). It binds directly to the U6 snRNA and plays a role in the biogenesis and stability of the U6 snRNP and U4/U6 snRNP complexes. It probably also is involved degradation of nuclear pre-mRNA by targeting them for decapping. LSM3 binds specifically to the 3'-terminal U-tract of U6 snRNA. LSM2-LSM8 probably is involved in processing of pre-tRNAs, pre-rRNAs and U3 snoRNA. LSM3, probably in a complex that contains LSM2-LSM7 but not LSM1 or LSM8, associates with the precursor of the RNA component of RNase P (pre-P RNA) and may be involved in maturing pre-P RNA. LSM3 is required for processing of pre-tRNAs, pre-rRNAs and U3 snoRNA.<ref>PMID:7744014</ref> <ref>PMID:10747033</ref> <ref>PMID:10761922</ref> <ref>PMID:12077351</ref> <ref>PMID:12438310</ref> <ref>PMID:15485930</ref>  [[http://www.uniprot.org/uniprot/PRP21_YEAST PRP21_YEAST]] mRNA splicing factors, PRP9, PRP11, and PRP21, are necessary for binding of the U2 snRNP to the pre-mRNA in an early step of spliceosome assembly. [[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/LSM5_YEAST LSM5_YEAST]] Component of LSm protein complexes, which are involved in RNA processing and may function in a chaperone-like manner. Component of the cytoplasmic LSM1-LSM7 complex which is thought to be involved in mRNA degradation by activating the decapping step. Component of the nuclear LSM2-LSM8 complex, which is involved in splicing of nuclear mRNAs. LSM2-LSM8 associates with multiple snRNP complexes containing the U6 snRNA (U4/U6 snRNP, U4/U6.U5 snRNP, and free U6 snRNP). It binds directly to the U6 snRNA and plays a role in the biogenesis and stability of the U6 snRNP and U4/U6 snRNP complexes. It probably also is involved degradation of nuclear pre-mRNA by targeting them for decapping. LSM5 binds specifically to the 3'-terminal U-tract of U6 snRNA. LSM2-LSM8 probably is involved in processing of pre-tRNAs, pre-rRNAs and U3 snoRNA. LSM5, probably in a complex that contains LSM2-LSM7 but not LSM1 or LSM8, associates with the precursor of the RNA component of RNase P (pre-P RNA) and may be involved in maturing pre-P RNA. LSM5 is required for processing of pre-tRNAs, pre-rRNAs and U3 snoRNA.<ref>PMID:10747033</ref> <ref>PMID:10761922</ref> <ref>PMID:12077351</ref> <ref>PMID:12438310</ref> <ref>PMID:15485930</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/DIB1_YEAST DIB1_YEAST]] Essential role in pre-mRNA splicing. Also essential for entry into mitosis (G2/M progression) as well as for chromosome segregation during mitosis. [[http://www.uniprot.org/uniprot/CWC26_YEAST CWC26_YEAST]] Required for efficient splicing and pre-mRNA nuclear retention. May also be involved in positioning the proximal bud pole signal.<ref>PMID:8657162</ref> <ref>PMID:11452010</ref> <ref>PMID:12871902</ref> <ref>PMID:15565172</ref>  [[http://www.uniprot.org/uniprot/PRP31_YEAST PRP31_YEAST]] Promotes the association of the U4/U6.U5 tri-snRNP particle with pre-spliceosomes to form the mature spliceosomal complex.<ref>PMID:8604353</ref>  [[http://www.uniprot.org/uniprot/RDS3_YEAST RDS3_YEAST]] Required for pre-mRNA splicing. Involved in regulation of drug sensitivity and may play a role in multidrug resistance.<ref>PMID:11943786</ref> <ref>PMID:14517302</ref>  [[http://www.uniprot.org/uniprot/LSM8_YEAST LSM8_YEAST]] Component of the nuclear LSM2-LSM8 complex, which is involved in splicing of nuclear mRNAs. LSM2-LSM8 associates with multiple snRNP complexes containing the U6 snRNA (U4/U6 snRNP, spliceosomal U4/U6.U5 snRNP, and free U6 snRNP). It binds directly to the U6 snRNA and plays a role in the biogenesis and stability of the U6 snRNP and U4/U6 snRNP complexes. It probably also is involved degradation of nuclear pre-mRNA by targeting them for decapping. LSM2-LSM8 probably is involved in processing of pre-tRNAs, pre-rRNAs and U3 snoRNA. LSM2 is required for processing of pre-tRNAs, pre-rRNAs and U3 snoRNA.<ref>PMID:12077351</ref> <ref>PMID:12438310</ref> <ref>PMID:15485930</ref>  [[http://www.uniprot.org/uniprot/PRP9_YEAST PRP9_YEAST]] mRNA splicing factors, PRP9, PRP11, and PRP21, are necessary for binding of the U2 snRNP to the pre-mRNA in an early step of spliceosome assembly. [[http://www.uniprot.org/uniprot/LSM6_YEAST LSM6_YEAST]] Component of LSm protein complexes, which are involved in RNA processing and may function in a chaperone-like manner, facilitating the efficient association of RNA processing factors with their substrates. Component of the cytoplasmic LSM1-LSM7 complex, which is thought to be involved in mRNA degradation by activating the decapping step in the 5'-to-3' mRNA decay pathway. In association with PAT1, LSM1-LSM7 binds directly to RNAs near the 3'-end and prefers oligoadenylated RNAs over polyadenylated RNAs. Component of the nuclear LSM2-LSM8 complex, which is involved in splicing of nuclear mRNAs. LSM2-LSM8 associates with multiple snRNP complexes containing the U6 snRNA (U4/U6 di-snRNP, spliceosomal U4/U6.U5 tri-snRNP, and free U6 snRNP). It binds directly to the 3'-terminal U-tract of U6 snRNA and plays a role in the biogenesis and stability of the U6 snRNP and U4/U6 snRNP complexes. LSM2-LSM8 probably also is involved degradation of nuclear pre-mRNA by targeting them for decapping, and in processing of pre-tRNAs, pre-rRNAs and U3 snoRNA. Component of a nucleolar LSM2-LSM7 complex, which associates with the precursor of the RNA component of RNase P (pre-P RNA) and with the small nucleolar RNA (snoRNA) snR5. It may play a role in the maturation of a subset of nucleolus-associated small RNAs.<ref>PMID:10747033</ref> <ref>PMID:10761922</ref> <ref>PMID:15485930</ref> <ref>PMID:17513695</ref>  [[http://www.uniprot.org/uniprot/LSM4_YEAST LSM4_YEAST]] Component of LSm protein complexes, which are involved in RNA processing and may function in a chaperone-like manner. Component of the cytoplasmic LSM1-LSM7 complex which is thought to be involved in mRNA degradation by activating the decapping step. Component of the nuclear LSM2-LSM8 complex, which is involved in splicing of nuclear mRNAs. LSM2-LSM8 associates with multiple spliceosome snRNP complexes containing the U6 snRNA (U4/U6 snRNP, U4/U6.U5 snRNP, and free U6 snRNP). It binds directly to the U6 snRNA and plays a role in the biogenesis and stability of the U6 snRNP and U4/U6 snRNP complexes. It probably also is involved degradation of nuclear pre-mRNA by targeting them for decapping. LSM4 binds specifically to the 3'-terminal U-tract of U6 snRNA. LSM2-LSM8 probably is involved in processing of pre-tRNAs, pre-rRNAs and U3 snoRNA. LSM4, probably in a complex that contains LSM2-LSM7 but not LSM1 or LSM8, associates with the precursor of the RNA component of RNase P (pre-P RNA) and may be involved in maturing pre-P RNA. LSM4 is required for processing of pre-tRNAs, pre-rRNAs and U3 snoRNA.<ref>PMID:10747033</ref> <ref>PMID:10761922</ref> <ref>PMID:12077351</ref> <ref>PMID:12438310</ref> <ref>PMID:15485930</ref>  [[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/IST3_YEAST IST3_YEAST]] Required for pre-mRNA splicing and spliceosome assembly. As part of the pre-mRNA retention and splicing (RES) complex, required for nuclear pre-mRNA retention and efficient splicing. Required for MER1-activated splicing.<ref>PMID:11287609</ref> <ref>PMID:15565172</ref> <ref>PMID:14973223</ref>  [[http://www.uniprot.org/uniprot/PRP6_YEAST PRP6_YEAST]] Participates in pre-mRNA splicing. Part of the U4/U5/U6 tri-snRNP complex, one of the building blocks of the spliceosome. [[http://www.uniprot.org/uniprot/RSE1_YEAST RSE1_YEAST]] Involved in G2/M transition (By similarity). Required for pre-mRNA splicing and endoplasmic reticulum (ER) to Golgi secretion pathway. U2 snRNPs associated protein required for the pre-spliceosome assembly. The involvement in ER to Golgi secretion is probably indirect and due to the splicing of the pre-mRNA coding for SAR1, a small GTP-binding protein required for COPII vesicle formation from the ER.<ref>PMID:10369685</ref> <ref>PMID:9819400</ref>  [[http://www.uniprot.org/uniprot/YSF3_YEAST YSF3_YEAST]] Involved in pre-mRNA splicing. Required for the SF3b integrity and prespliceosome assembly.<ref>PMID:16314500</ref>  [[http://www.uniprot.org/uniprot/PRP11_YEAST PRP11_YEAST]] mRNA splicing factors, PRP9, PRP11, and PRP21, are necessary for addition of the U2 snRNP to the pre-mRNA in an early step of spliceosome assembly.<ref>PMID:9710584</ref>  [[http://www.uniprot.org/uniprot/SNU66_YEAST SNU66_YEAST]] Component of the U4/U6.U5 tri-snRNP particle, one of the building blocks of the spliceosome. Required for pre-mRNA splicing.<ref>PMID:11290703</ref>  [[http://www.uniprot.org/uniprot/PRP3_YEAST PRP3_YEAST]] Participates in pre-mRNA splicing. Part of the U4/U5/U6 tri-snRNP complex, one of the building blocks of the spliceosome.<ref>PMID:9326489</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The precatalytic spliceosome (B complex) is preceded by the pre-B complex. Here we report the cryo-electron microscopy structures of the Saccharomyces cerevisiae pre-B and B complexes at average resolutions of 3.3 to 4.6 and 3.9 angstroms, respectively. In the pre-B complex, the duplex between the 5' splice site (5'SS) and U1 small nuclear RNA (snRNA) is recognized by Yhc1, Luc7, and the Sm ring. In the B complex, U1 small nuclear ribonucleoprotein is dissociated, the 5'-exon-5'SS sequences are translocated near U6 snRNA, and three B-specific proteins may orient the precursor messenger RNA. In both complexes, U6 snRNA is anchored to loop I of U5 snRNA, and the duplex between the branch point sequence and U2 snRNA is recognized by the SF3b complex. Structural analysis reveals the mechanism of assembly and activation for the yeast spliceosome.

Structures of the fully assembled Saccharomyces cerevisiae spliceosome before activation.,Bai R, Wan R, Yan C, Lei J, Shi Y Science. 2018 Jun 29;360(6396):1423-1429. doi: 10.1126/science.aau0325. Epub 2018, May 24. PMID:29794219<ref>PMID:29794219</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5zwm" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</SX>
[[Category: Large Structures]]
[[Category: RNA helicase]]
[[Category: Saccharomyces cerevisiae s288c]]
[[Category: Bai, R]]
[[Category: Lei, J]]
[[Category: Shi, Y]]
[[Category: Wan, R]]
[[Category: Yan, C]]
[[Category: Assembly]]
[[Category: Pre-b complex]]
[[Category: Spliceosome]]
[[Category: Splicing]]
[[Category: U1 snrnp]]