7oqb: Difference between revisions
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==== | ==The U2 part of Saccharomyces cerevisiae spliceosomal pre-A complex (delta BS-A ACT1)== | ||
<StructureSection load='7oqb' size='340' side='right'caption='[[7oqb]]' scene=''> | <StructureSection load='7oqb' size='340' side='right'caption='[[7oqb]], [[Resolution|resolution]] 9.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | <table><tr><td colspan='2'>[[7oqb]] 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=7OQB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OQB FirstGlance]. <br> | ||
</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=7oqb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7oqb OCA], [https://pdbe.org/7oqb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7oqb RCSB], [https://www.ebi.ac.uk/pdbsum/7oqb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7oqb ProSAT]</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]] 9Å</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=7oqb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7oqb OCA], [https://pdbe.org/7oqb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7oqb RCSB], [https://www.ebi.ac.uk/pdbsum/7oqb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7oqb ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/SF3B1_YEAST SF3B1_YEAST] Contacts pre-mRNA on both sides of the branch site early in spliceosome assembly. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
During the splicing of introns from precursor messenger RNAs (pre-mRNAs), the U2 small nuclear ribonucleoprotein (snRNP) must undergo stable integration into the spliceosomal A complex-a poorly understood, multistep process that is facilitated by the DEAD-box helicase Prp5 (refs. (1-4)). During this process, the U2 small nuclear RNA (snRNA) forms an RNA duplex with the pre-mRNA branch site (the U2-BS helix), which is proofread by Prp5 at this stage through an unclear mechanism(5). Here, by deleting the branch-site adenosine (BS-A) or mutating the branch-site sequence of an actin pre-mRNA, we stall the assembly of spliceosomes in extracts from the yeast Saccharomyces cerevisiae directly before the A complex is formed. We then determine the three-dimensional structure of this newly identified assembly intermediate by cryo-electron microscopy. Our structure indicates that the U2-BS helix has formed in this pre-A complex, but is not yet clamped by the HEAT domain of the Hsh155 protein (Hsh155(HEAT)), which exhibits an open conformation. The structure further reveals a large-scale remodelling/repositioning of the U1 and U2 snRNPs during the formation of the A complex that is required to allow subsequent binding of the U4/U6.U5 tri-snRNP, but that this repositioning is blocked in the pre-A complex by the presence of Prp5. Our data suggest that binding of Hsh155(HEAT) to the bulged BS-A of the U2-BS helix triggers closure of Hsh155(HEAT), which in turn destabilizes Prp5 binding. Thus, Prp5 proofreads the branch site indirectly, hindering spliceosome assembly if branch-site mutations prevent the remodelling of Hsh155(HEAT). Our data provide structural insights into how a spliceosomal helicase enhances the fidelity of pre-mRNA splicing. | |||
Structural insights into how Prp5 proofreads the pre-mRNA branch site.,Zhang Z, Rigo N, Dybkov O, Fourmann JB, Will CL, Kumar V, Urlaub H, Stark H, Luhrmann R Nature. 2021 Aug;596(7871):296-300. doi: 10.1038/s41586-021-03789-5. Epub 2021, Aug 4. PMID:34349264<ref>PMID:34349264</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7oqb" 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__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Z | [[Category: Saccharomyces cerevisiae]] | ||
[[Category: Dybkov O]] | |||
[[Category: Fourmann J]] | |||
[[Category: Kumar V]] | |||
[[Category: Luehrmann R]] | |||
[[Category: Rigo N]] | |||
[[Category: Stark H]] | |||
[[Category: Urlaub H]] | |||
[[Category: Will CL]] | |||
[[Category: Zhang Z]] | |||
Latest revision as of 15:28, 17 July 2024
The U2 part of Saccharomyces cerevisiae spliceosomal pre-A complex (delta BS-A ACT1)The U2 part of Saccharomyces cerevisiae spliceosomal pre-A complex (delta BS-A ACT1)
Structural highlights
FunctionSF3B1_YEAST Contacts pre-mRNA on both sides of the branch site early in spliceosome assembly. Publication Abstract from PubMedDuring the splicing of introns from precursor messenger RNAs (pre-mRNAs), the U2 small nuclear ribonucleoprotein (snRNP) must undergo stable integration into the spliceosomal A complex-a poorly understood, multistep process that is facilitated by the DEAD-box helicase Prp5 (refs. (1-4)). During this process, the U2 small nuclear RNA (snRNA) forms an RNA duplex with the pre-mRNA branch site (the U2-BS helix), which is proofread by Prp5 at this stage through an unclear mechanism(5). Here, by deleting the branch-site adenosine (BS-A) or mutating the branch-site sequence of an actin pre-mRNA, we stall the assembly of spliceosomes in extracts from the yeast Saccharomyces cerevisiae directly before the A complex is formed. We then determine the three-dimensional structure of this newly identified assembly intermediate by cryo-electron microscopy. Our structure indicates that the U2-BS helix has formed in this pre-A complex, but is not yet clamped by the HEAT domain of the Hsh155 protein (Hsh155(HEAT)), which exhibits an open conformation. The structure further reveals a large-scale remodelling/repositioning of the U1 and U2 snRNPs during the formation of the A complex that is required to allow subsequent binding of the U4/U6.U5 tri-snRNP, but that this repositioning is blocked in the pre-A complex by the presence of Prp5. Our data suggest that binding of Hsh155(HEAT) to the bulged BS-A of the U2-BS helix triggers closure of Hsh155(HEAT), which in turn destabilizes Prp5 binding. Thus, Prp5 proofreads the branch site indirectly, hindering spliceosome assembly if branch-site mutations prevent the remodelling of Hsh155(HEAT). Our data provide structural insights into how a spliceosomal helicase enhances the fidelity of pre-mRNA splicing. Structural insights into how Prp5 proofreads the pre-mRNA branch site.,Zhang Z, Rigo N, Dybkov O, Fourmann JB, Will CL, Kumar V, Urlaub H, Stark H, Luhrmann R Nature. 2021 Aug;596(7871):296-300. doi: 10.1038/s41586-021-03789-5. Epub 2021, Aug 4. PMID:34349264[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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