8r08: Difference between revisions
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The entry | ==Cryo-EM structure of the cross-exon pre-B+AMPPNP complex== | ||
<StructureSection load='8r08' size='340' side='right'caption='[[8r08]], [[Resolution|resolution]] 6.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8r08]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8R08 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8R08 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]] 6.1Å</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=8r08 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8r08 OCA], [https://pdbe.org/8r08 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8r08 RCSB], [https://www.ebi.ac.uk/pdbsum/8r08 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8r08 ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/U5S1_HUMAN U5S1_HUMAN] Mandibulofacial dysostosis-microcephaly syndrome. The disease is caused by mutations affecting the gene represented in this entry. | |||
== Function == | |||
[https://www.uniprot.org/uniprot/U5S1_HUMAN U5S1_HUMAN] Component of the U5 snRNP and the U4/U6-U5 tri-snRNP complex required for pre-mRNA splicing. Binds GTP. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Early spliceosome assembly can occur through an intron-defined pathway, whereby U1 and U2 small nuclear ribonucleoprotein particles (snRNPs) assemble across the intron(1). Alternatively, it can occur through an exon-defined pathway(2-5), whereby U2 binds the branch site located upstream of the defined exon and U1 snRNP interacts with the 5' splice site located directly downstream of it. The U4/U6.U5 tri-snRNP subsequently binds to produce a cross-intron (CI) or cross-exon (CE) pre-B complex, which is then converted to the spliceosomal B complex(6,7). Exon definition promotes the splicing of upstream introns(2,8,9) and plays a key part in alternative splicing regulation(10-16). However, the three-dimensional structure of exon-defined spliceosomal complexes and the molecular mechanism of the conversion from a CE-organized to a CI-organized spliceosome, a pre-requisite for splicing catalysis, remain poorly understood. Here cryo-electron microscopy analyses of human CE pre-B complex and B-like complexes reveal extensive structural similarities with their CI counterparts. The results indicate that the CE and CI spliceosome assembly pathways converge already at the pre-B stage. Add-back experiments using purified CE pre-B complexes, coupled with cryo-electron microscopy, elucidate the order of the extensive remodelling events that accompany the formation of B complexes and B-like complexes. The molecular triggers and roles of B-specific proteins in these rearrangements are also identified. We show that CE pre-B complexes can productively bind in trans to a U1 snRNP-bound 5' splice site. Together, our studies provide new mechanistic insights into the CE to CI switch during spliceosome assembly and its effect on pre-mRNA splice site pairing at this stage. | |||
Structural insights into the cross-exon to cross-intron spliceosome switch.,Zhang Z, Kumar V, Dybkov O, Will CL, Zhong J, Ludwig SEJ, Urlaub H, Kastner B, Stark H, Luhrmann R Nature. 2024 May 22. doi: 10.1038/s41586-024-07458-1. PMID:38778104<ref>PMID:38778104</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8r08" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Dybkov O]] | |||
[[Category: Kastner B]] | |||
[[Category: Kumar V]] | |||
[[Category: Ludwig S]] | |||
[[Category: Luehrmann R]] | |||
[[Category: Stark H]] | |||
[[Category: Urlaub H]] | |||
[[Category: Will CL]] | |||
[[Category: Zhang Z]] | |||
[[Category: Zhong J]] | |||