View source for 8ffy


==Cryo-electron microscopy structure of human mt-SerRS in complex with mt-tRNA(UGA-TL)==
<StructureSection load='8ffy' size='340' side='right'caption='[[8ffy]], [[Resolution|resolution]] 3.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8ffy]] is a 3 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=8FFY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FFY 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]] 3.6&#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>, <scene name='pdbligand=SSA:5-O-(N-(L-SERYL)-SULFAMOYL)ADENOSINE'>SSA</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=8ffy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ffy OCA], [https://pdbe.org/8ffy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ffy RCSB], [https://www.ebi.ac.uk/pdbsum/8ffy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ffy ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/SYSM_HUMAN SYSM_HUMAN] Hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome. The disease is caused by variants affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/SYSM_HUMAN SYSM_HUMAN] Catalyzes the attachment of serine to tRNA(Ser). Is also probably able to aminoacylate tRNA(Sec) with serine, to form the misacylated tRNA L-seryl-tRNA(Sec), which will be further converted into selenocysteinyl-tRNA(Sec).[UniProtKB:Q9N0F3]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Animal mitochondrial gene expression relies on specific interactions between nuclear-encoded aminoacyl-tRNA synthetases and mitochondria-encoded tRNAs. Their evolution involves an antagonistic interplay between strong mutation pressure on mtRNAs and selection pressure to maintain their essential function. To understand the molecular consequences of this interplay, we analyze the human mitochondrial serylation system, in which one synthetase charges two highly divergent mtRNA(Ser) isoacceptors. We present the cryo-EM structure of human mSerRS in complex with mtRNA(Ser(UGA)), and perform a structural and functional comparison with the mSerRS-mtRNA(Ser(GCU)) complex. We find that despite their common function, mtRNA(Ser(UGA)) and mtRNA(Ser(GCU)) show no constrain to converge on shared structural or sequence identity motifs for recognition by mSerRS. Instead, mSerRS evolved a bimodal readout mechanism, whereby a single protein surface recognizes degenerate identity features specific to each mtRNA(Ser). Our results show how the mutational erosion of mtRNAs drove a remarkable innovation of intermolecular specificity rules, with multiple evolutionary pathways leading to functionally equivalent outcomes.

Structural basis for a degenerate tRNA identity code and the evolution of bimodal specificity in human mitochondrial tRNA recognition.,Kuhle B, Hirschi M, Doerfel LK, Lander GC, Schimmel P Nat Commun. 2023 Aug 9;14(1):4794. doi: 10.1038/s41467-023-40354-2. PMID:37558671<ref>PMID:37558671</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8ffy" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Doerfel L]]
[[Category: Hirschi M]]
[[Category: Kuhle B]]
[[Category: Lander G]]
[[Category: Schimmel P]]