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The entry | ==Rabbit 80S ribosome stalled close to the mutated SARS-CoV-2 slippery site by a pseudoknot (classified for pseudoknot)== | ||
<StructureSection load='7o7z' size='340' side='right'caption='[[7o7z]], [[Resolution|resolution]] 2.40Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7o7z]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7O7Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7O7Z 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]] 2.4Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1MA:6-HYDRO-1-METHYLADENOSINE-5-MONOPHOSPHATE'>1MA</scene>, <scene name='pdbligand=2MG:2N-METHYLGUANOSINE-5-MONOPHOSPHATE'>2MG</scene>, <scene name='pdbligand=4AC:N(4)-ACETYLCYTIDINE-5-MONOPHOSPHATE'>4AC</scene>, <scene name='pdbligand=5MC:5-METHYLCYTIDINE-5-MONOPHOSPHATE'>5MC</scene>, <scene name='pdbligand=5MU:5-METHYLURIDINE+5-MONOPHOSPHATE'>5MU</scene>, <scene name='pdbligand=6MZ:N6-METHYLADENOSINE-5-MONOPHOSPHATE'>6MZ</scene>, <scene name='pdbligand=A2M:2-O-METHYLADENOSINE+5-(DIHYDROGEN+PHOSPHATE)'>A2M</scene>, <scene name='pdbligand=AAC:ACETYLAMINO-ACETIC+ACID'>AAC</scene>, <scene name='pdbligand=AME:N-ACETYLMETHIONINE'>AME</scene>, <scene name='pdbligand=AYA:N-ACETYLALANINE'>AYA</scene>, <scene name='pdbligand=B8N:(2~{R})-2-azanyl-4-[5-[(2~{S},3~{R},4~{S},5~{R})-3,4-bis(oxidanyl)-5-(phosphonooxymethyl)oxolan-2-yl]-3-methyl-2,6-bis(oxidanylidene)pyrimidin-1-yl]butanoic+acid'>B8N</scene>, <scene name='pdbligand=G7M:N7-METHYL-GUANOSINE-5-MONOPHOSPHATE'>G7M</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=H2U:5,6-DIHYDROURIDINE-5-MONOPHOSPHATE'>H2U</scene>, <scene name='pdbligand=HIC:4-METHYL-HISTIDINE'>HIC</scene>, <scene name='pdbligand=HY3:3-HYDROXYPROLINE'>HY3</scene>, <scene name='pdbligand=M2G:N2-DIMETHYLGUANOSINE-5-MONOPHOSPHATE'>M2G</scene>, <scene name='pdbligand=M3L:N-TRIMETHYLLYSINE'>M3L</scene>, <scene name='pdbligand=MA6:6N-DIMETHYLADENOSINE-5-MONOPHOSHATE'>MA6</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MLZ:N-METHYL-LYSINE'>MLZ</scene>, <scene name='pdbligand=N:ANY+5-MONOPHOSPHATE+NUCLEOTIDE'>N</scene>, <scene name='pdbligand=NMM:(2S)-2-AMINO-5-[(N-METHYLCARBAMIMIDOYL)AMINO]PENTANOIC+ACID'>NMM</scene>, <scene name='pdbligand=OMC:O2-METHYLYCYTIDINE-5-MONOPHOSPHATE'>OMC</scene>, <scene name='pdbligand=OMG:O2-METHYLGUANOSINE-5-MONOPHOSPHATE'>OMG</scene>, <scene name='pdbligand=OMU:O2-METHYLURIDINE+5-MONOPHOSPHATE'>OMU</scene>, <scene name='pdbligand=PSU:PSEUDOURIDINE-5-MONOPHOSPHATE'>PSU</scene>, <scene name='pdbligand=SAC:N-ACETYL-SERINE'>SAC</scene>, <scene name='pdbligand=SPD:SPERMIDINE'>SPD</scene>, <scene name='pdbligand=SPM:SPERMINE'>SPM</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene>, <scene name='pdbligand=UR3:3-METHYLURIDINE-5-MONOPHOSHATE'>UR3</scene>, <scene name='pdbligand=UY1:2-O-methylpseudouridine-5-monophosphate'>UY1</scene>, <scene name='pdbligand=V5N:(2S,3S)-2-azanyl-3-(1H-imidazol-5-yl)-3-oxidanyl-propanoic+acid'>V5N</scene>, <scene name='pdbligand=YYG:4-(3-[5-O-PHOSPHONORIBOFURANOSYL]-4,6-DIMETHYL-8-OXO-4,8-DIHYDRO-3H-1,3,4,5,7A-PENTAAZA-S-INDACEN-YLAMINO-BUTYRIC+ACID+METHYL+ESTER'>YYG</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=7o7z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7o7z OCA], [https://pdbe.org/7o7z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7o7z RCSB], [https://www.ebi.ac.uk/pdbsum/7o7z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7o7z ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/G1TZ76_RABIT G1TZ76_RABIT] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Programmed ribosomal frameshifting is a key event during translation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA genome that allows synthesis of the viral RNA-dependent RNA polymerase and downstream proteins. Here, we present the cryo-electron microscopy structure of a translating mammalian ribosome primed for frameshifting on the viral RNA. The viral RNA adopts a pseudoknot structure that lodges at the entry to the ribosomal messenger RNA (mRNA) channel to generate tension in the mRNA and promote frameshifting, whereas the nascent viral polyprotein forms distinct interactions with the ribosomal tunnel. Biochemical experiments validate the structural observations and reveal mechanistic and regulatory features that influence frameshifting efficiency. Finally, we compare compounds previously shown to reduce frameshifting with respect to their ability to inhibit SARS-CoV-2 replication, establishing coronavirus frameshifting as a target for antiviral intervention. | |||
Structural basis of ribosomal frameshifting during translation of the SARS-CoV-2 RNA genome.,Bhatt PR, Scaiola A, Loughran G, Leibundgut M, Kratzel A, Meurs R, Dreos R, O'Connor KM, McMillan A, Bode JW, Thiel V, Gatfield D, Atkins JF, Ban N Science. 2021 Jun 18;372(6548):1306-1313. doi: 10.1126/science.abf3546. Epub 2021 , May 13. PMID:34029205<ref>PMID:34029205</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7o7z" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Ribosome 3D structures|Ribosome 3D structures]] | |||
*[[3D sructureseceptor for activated protein kinase C 1|3D sructureseceptor for activated protein kinase C 1]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Bos taurus]] | |||
[[Category: Large Structures]] | |||
[[Category: Oryctolagus cuniculus]] | |||
[[Category: Atkins JF]] | |||
[[Category: Ban N]] | |||
[[Category: Bhatt PR]] | |||
[[Category: Leibundgut MA]] | |||
[[Category: Scaiola A]] | |||
Latest revision as of 14:02, 15 November 2023
Rabbit 80S ribosome stalled close to the mutated SARS-CoV-2 slippery site by a pseudoknot (classified for pseudoknot)Rabbit 80S ribosome stalled close to the mutated SARS-CoV-2 slippery site by a pseudoknot (classified for pseudoknot)
Structural highlights
FunctionPublication Abstract from PubMedProgrammed ribosomal frameshifting is a key event during translation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA genome that allows synthesis of the viral RNA-dependent RNA polymerase and downstream proteins. Here, we present the cryo-electron microscopy structure of a translating mammalian ribosome primed for frameshifting on the viral RNA. The viral RNA adopts a pseudoknot structure that lodges at the entry to the ribosomal messenger RNA (mRNA) channel to generate tension in the mRNA and promote frameshifting, whereas the nascent viral polyprotein forms distinct interactions with the ribosomal tunnel. Biochemical experiments validate the structural observations and reveal mechanistic and regulatory features that influence frameshifting efficiency. Finally, we compare compounds previously shown to reduce frameshifting with respect to their ability to inhibit SARS-CoV-2 replication, establishing coronavirus frameshifting as a target for antiviral intervention. Structural basis of ribosomal frameshifting during translation of the SARS-CoV-2 RNA genome.,Bhatt PR, Scaiola A, Loughran G, Leibundgut M, Kratzel A, Meurs R, Dreos R, O'Connor KM, McMillan A, Bode JW, Thiel V, Gatfield D, Atkins JF, Ban N Science. 2021 Jun 18;372(6548):1306-1313. doi: 10.1126/science.abf3546. Epub 2021 , May 13. PMID:34029205[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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