View source for 8hmy


==Cryo-EM structure of the human pre-catalytic TSEN/pre-tRNA complex==
<StructureSection load='8hmy' size='340' side='right'caption='[[8hmy]], [[Resolution|resolution]] 2.94&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8hmy]] is a 6 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=8HMY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8HMY 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]] 2.94&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=8hmy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8hmy OCA], [https://pdbe.org/8hmy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8hmy RCSB], [https://www.ebi.ac.uk/pdbsum/8hmy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8hmy ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/SEN2_HUMAN SEN2_HUMAN] Pontocerebellar hypoplasia type 2. The disease is caused by variants affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/SEN2_HUMAN SEN2_HUMAN] Constitutes one of the two catalytic subunit of the tRNA-splicing endonuclease complex, a complex responsible for identification and cleavage of the splice sites in pre-tRNA. It cleaves pre-tRNA at the 5'- and 3'-splice sites to release the intron. The products are an intron and two tRNA half-molecules bearing 2',3'-cyclic phosphate and 5'-OH termini. There are no conserved sequences at the splice sites, but the intron is invariably located at the same site in the gene, placing the splice sites an invariant distance from the constant structural features of the tRNA body. Isoform 1 probably carries the active site for 5'-splice site cleavage. The tRNA splicing endonuclease is also involved in mRNA processing via its association with pre-mRNA 3'-end processing factors, establishing a link between pre-tRNA splicing and pre-mRNA 3'-end formation, suggesting that the endonuclease subunits function in multiple RNA-processing events. Isoform 2 is responsible for processing a yet unknown RNA substrate. The complex containing isoform 2 is not able to cleave pre-tRNAs properly, although it retains endonucleolytic activity.<ref>PMID:15109492</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Removal of the intron from precursor-tRNA (pre-tRNA) is essential in all three kingdoms of life. In humans, this process is mediated by the tRNA splicing endonuclease (TSEN) comprising four subunits: TSEN2, TSEN15, TSEN34, and TSEN54. Here, we report the cryo-EM structures of human TSEN bound to full-length pre-tRNA in the pre-catalytic and post-catalytic states at average resolutions of 2.94 and 2.88 A, respectively. Human TSEN features an extended surface groove that holds the L-shaped pre-tRNA. The mature domain of pre-tRNA is recognized by conserved structural elements of TSEN34, TSEN54, and TSEN2. Such recognition orients the anticodon stem of pre-tRNA and places the 3'-splice site and 5'-splice site into the catalytic centers of TSEN34 and TSEN2, respectively. The bulk of the intron sequences makes no direct interaction with TSEN, explaining why pre-tRNAs of varying introns can be accommodated and cleaved. Our structures reveal the molecular ruler mechanism of pre-tRNA cleavage by TSEN.

Structural basis of pre-tRNA intron removal by human tRNA splicing endonuclease.,Zhang X, Yang F, Zhan X, Bian T, Xing Z, Lu Y, Shi Y Mol Cell. 2023 Apr 20;83(8):1328-1339.e4. doi: 10.1016/j.molcel.2023.03.015. Epub , 2023 Apr 6. PMID:37028420<ref>PMID:37028420</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8hmy" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Shi Y]]
[[Category: Yang F]]
[[Category: Zhan X]]
[[Category: Zhang X]]