View source for 7oqc


==The U1 part of Saccharomyces cerevisiae spliceosomal pre-A complex (delta BS-A ACT1)==
<StructureSection load='7oqc' size='340' side='right'caption='[[7oqc]], [[Resolution|resolution]] 4.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7oqc]] 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=7OQC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OQC FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=N:ANY+5-MONOPHOSPHATE+NUCLEOTIDE'>N</scene></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=7oqc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7oqc OCA], [https://pdbe.org/7oqc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7oqc RCSB], [https://www.ebi.ac.uk/pdbsum/7oqc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7oqc ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NAM8_YEAST NAM8_YEAST] Acts as a suppressor of mitochondrial splicing deficiencies when overexpressed. Could be a non-essential component of the mitochondrial splicing machinery.
<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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 7oqc" style="background-color:#fffaf0;"></div>

==See Also==
*[[Nucleoprotein 3D structures|Nucleoprotein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[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]]