9ru7: Difference between revisions
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==WT-HEK 80S ribosome bound to Kozak mRNA (WT-Kozak)== | |||
<StructureSection load='9ru7' size='340' side='right'caption='[[9ru7]], [[Resolution|resolution]] 3.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9ru7]] 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=9RU7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9RU7 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]] 3Å</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=4SU:4-THIOURIDINE-5-MONOPHOSPHATE'>4SU</scene>, <scene name='pdbligand=5MC:5-METHYLCYTIDINE-5-MONOPHOSPHATE'>5MC</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=G7M:N7-METHYL-GUANOSINE-5-MONOPHOSPHATE'>G7M</scene>, <scene name='pdbligand=H2U:5,6-DIHYDROURIDINE-5-MONOPHOSPHATE'>H2U</scene>, <scene name='pdbligand=HIC:4-METHYL-HISTIDINE'>HIC</scene>, <scene name='pdbligand=HYG:HYGROMYCIN+B'>HYG</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=M3L:N-TRIMETHYLLYSINE'>M3L</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MLZ:N-METHYL-LYSINE'>MLZ</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=UR3:3-METHYLURIDINE-5-MONOPHOSHATE'>UR3</scene>, <scene name='pdbligand=V5N:(2~{S},3~{S})-2-azanyl-3-(1~{H}-imidazol-5-yl)-3-oxidanyl-propanoic+acid'>V5N</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=9ru7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9ru7 OCA], [https://pdbe.org/9ru7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9ru7 RCSB], [https://www.ebi.ac.uk/pdbsum/9ru7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9ru7 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/RS15_HUMAN RS15_HUMAN] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The ribosome mRNA channel is central to translation, yet its role in regulatory mechanisms remains unclear. Using cryo-EM of human ribosomal complexes bound to Kozak and TISU mRNAs from wild-type (WT) and RPS26/eS26 mutant (RPS26dC) cells, we demonstrate that both RPS26/eS26 and mRNA adopt distinct conformations, explaining the opposing effects of RPS26dC on their activity. Translatome studies of WT and RPS26dC reveal AUG-context-dependent changes in 48S and 80S initiation complexes and slower scanning. Downregulated mRNAs are enriched for specific AUG-upstream nucleotides and a -1-cytosine contacting 18S rRNA G1207, an interaction lost in RPS26dC. Strongly affected transcripts include replication-dependent histones, which, despite short 5'UTRs and suboptimal Kozak, exhibit robust translation activity that is RPS26/eS26-dependent. We identify a translational enhancer in the H2B 5'UTR (-16 to -9) overlapping predicted RPS26/eS26-binding sites, with a distinct ribosome-bound conformation. Exploiting these features, we engineered a high-efficiency translational cassette with minimal leaky scanning. These findings underscore the role of the ribosome's mRNA channel in selective translation and its therapeutic potential. | |||
Structural and molecular basis of specialized translation mediated by the ribosome mRNA-binding channel.,Fraticelli D, Hiregange DG, Weiss B, Ogran A, Havkin-Solomon T, Roman IM, Bashan A, Yonath A, Dikstein R Nat Commun. 2026 Apr 29. doi: 10.1038/s41467-026-72263-5. PMID:42056121<ref>PMID:42056121</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 9ru7" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Bashan A]] | |||
[[Category: Dikstein R]] | |||
[[Category: Fraticelli D]] | |||
[[Category: Hiregange DG]] | |||
[[Category: Yonath A]] | |||
Latest revision as of 03:44, 14 May 2026
WT-HEK 80S ribosome bound to Kozak mRNA (WT-Kozak)
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