View source for 8c6j


==Human spliceosomal PM5 C* complex==
<StructureSection load='8c6j' size='340' side='right'caption='[[8c6j]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8c6j]] 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=8C6J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8C6J 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]] 2.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <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=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=8c6j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8c6j OCA], [https://pdbe.org/8c6j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8c6j RCSB], [https://www.ebi.ac.uk/pdbsum/8c6j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8c6j ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RBM8A_HUMAN RBM8A_HUMAN] Component of a splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of a few core proteins and several more peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Core components of the EJC, that remains bound to spliced mRNAs throughout all stages of mRNA metabolism, functions to mark the position of the exon-exon junction in the mature mRNA and thereby influences downstream processes of gene expression including mRNA splicing, nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). The heterodimer MAGOH-RBM8A interacts with PYM that function to enhance the translation of EJC-bearing spliced mRNAs by recruiting them to the ribosomal 48S preinitiation complex. Remains associated with mRNAs in the cytoplasm until the mRNAs engage the translation machinery. Its removal from cytoplasmic mRNAs requires translation initiation from EJC-bearing spliced mRNAs. Associates preferentially with mRNAs produced by splicing. Does not interact with pre-mRNAs, introns, or mRNAs produced from intronless cDNAs. Associates with both nuclear mRNAs and newly exported cytoplasmic mRNAs. Complex with MAGOH is a component of the nonsense mediated decay (NMD) pathway.<ref>PMID:12121612</ref> <ref>PMID:12718880</ref> <ref>PMID:12730685</ref> <ref>PMID:16209946</ref> <ref>PMID:19409878</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Alternative precursor messenger RNA splicing is instrumental in expanding the proteome of higher eukaryotes, and changes in 3' splice site (3'ss) usage contribute to human disease. We demonstrate by small interfering RNA-mediated knockdowns, followed by RNA sequencing, that many proteins first recruited to human C* spliceosomes, which catalyze step 2 of splicing, regulate alternative splicing, including the selection of alternatively spliced NAGNAG 3'ss. Cryo-electron microscopy and protein cross-linking reveal the molecular architecture of these proteins in C* spliceosomes, providing mechanistic and structural insights into how they influence 3'ss usage. They further elucidate the path of the 3' region of the intron, allowing a structure-based model for how the C* spliceosome potentially scans for the proximal 3'ss. By combining biochemical and structural approaches with genome-wide functional analyses, our studies reveal widespread regulation of alternative 3'ss usage after step 1 of splicing and the likely mechanisms whereby C* proteins influence NAGNAG 3'ss choices.

Regulation of 3' splice site selection after step 1 of splicing by spliceosomal C* proteins.,Dybkov O, Preussner M, El Ayoubi L, Feng VY, Harnisch C, Merz K, Leupold P, Yudichev P, Agafonov DE, Will CL, Girard C, Dienemann C, Urlaub H, Kastner B, Heyd F, Luhrmann R Sci Adv. 2023 Mar 3;9(9):eadf1785. doi: 10.1126/sciadv.adf1785. Epub 2023 Mar 3. PMID:36867703<ref>PMID:36867703</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8c6j" 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__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Dybkov O]]
[[Category: Kastner B]]
[[Category: Luehrmann R]]