View source for 7nwh


==Mammalian pre-termination 80S ribosome with eRF1 and eRF3 bound by Blasticidin S.==
<StructureSection load='7nwh' size='340' side='right'caption='[[7nwh]], [[Resolution|resolution]] 4.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7nwh]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NWH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NWH 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=BLS:BLASTICIDIN+S'>BLS</scene>, <scene name='pdbligand=GCP:PHOSPHOMETHYLPHOSPHONIC+ACID+GUANYLATE+ESTER'>GCP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=7nwh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nwh OCA], [https://pdbe.org/7nwh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nwh RCSB], [https://www.ebi.ac.uk/pdbsum/7nwh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nwh ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ERF1_RABIT ERF1_RABIT] Component of the eRF1-eRF3-GTP ternary complex, a ternary complex that mediates translation termination in response to the termination codons. The eRF1-eRF3-GTP complex binds to a stop codon in the ribosomal A-site. ETF1/ERF1 is responsible for stop codon recognition and inducing hydrolysis of peptidyl-tRNA. Following GTP hydrolysis, eRF3 (GSPT1/ERF3A or GSPT2/ERF3B) dissociates, permitting ETF1/eRF1 to accommodate fully in the A-site, followed by hydrolysis of peptidyl-tRNA. Component of the transient SURF complex which recruits UPF1 to stalled ribosomes in the context of nonsense-mediated decay (NMD) of mRNAs containing premature stop codons. Required for SHFL-mediated translation termination which inhibits programmed ribosomal frameshifting (-1PRF) of mRNA from viruses and cellular genes.[UniProtKB:P62495]
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== Publication Abstract from PubMed ==
Deciphering translation is of paramount importance for the understanding of many diseases, and antibiotics played a pivotal role in this endeavour. Blasticidin S (BlaS) targets translation by binding to the peptidyl transferase center of the large ribosomal subunit. Using biochemical, structural and cellular approaches, we show here that BlaS inhibits both translation elongation and termination in Mammalia. Bound to mammalian terminating ribosomes, BlaS distorts the 3'CCA tail of the P-site tRNA to a larger extent than previously reported for bacterial ribosomes, thus delaying both, peptide bond formation and peptidyl-tRNA hydrolysis. While BlaS does not inhibit stop codon recognition by the eukaryotic release factor 1 (eRF1), it interferes with eRF1's accommodation into the peptidyl transferase center and subsequent peptide release. In human cells, BlaS inhibits nonsense-mediated mRNA decay and, at subinhibitory concentrations, modulates translation dynamics at premature termination codons leading to enhanced protein production.

Blasticidin S inhibits mammalian translation and enhances production of protein encoded by nonsense mRNA.,Powers KT, Stevenson-Jones F, Yadav SKN, Amthor B, Bufton JC, Borucu U, Shen D, Becker JP, Lavysh D, Hentze MW, Kulozik AE, Neu-Yilik G, Schaffitzel C Nucleic Acids Res. 2021 Jul 21;49(13):7665-7679. doi: 10.1093/nar/gkab532. PMID:34157102<ref>PMID:34157102</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7nwh" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ribosome 3D structures|Ribosome 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Oryctolagus cuniculus]]
[[Category: Bufton JC]]
[[Category: Powers KT]]
[[Category: Schaffitzel C]]
[[Category: Yadav SKN]]