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==Crystal structure of T-2 toxin bound to the yeast 80S ribosome==
==Crystal structure of T-2 toxin bound to the yeast 80S ribosome==
<StructureSection load='4u6f' size='340' side='right' caption='[[4u6f]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
<StructureSection load='4u6f' size='340' side='right'caption='[[4u6f]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4u6f]] is a 162 chain structure with sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_atcc_204508_/_s288c Saccharomyces cerevisiae atcc 204508 / s288c]. This structure supersedes the now removed PDB entries and [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4ujy 4ujy]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4U6F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4U6F FirstGlance]. <br>
<table><tr><td colspan='2'>[[4u6f]] is a 20 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. This structure supersedes the now removed PDB entries [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4uju 4uju], [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4ujv 4ujv], [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4ujw 4ujw], [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4ujx 4ujx] and [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4ujy 4ujy]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4U6F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4U6F FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=OHX:OSMIUM+(III)+HEXAMMINE'>OHX</scene>, <scene name='pdbligand=ZBA:12,13-EPOXYTRICHOTHEC-9-ENE-3,4,8,15-TETROL-4,15-DIACETATE-8-ISOVALERATE'>ZBA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.1&#8491;</td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></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>, <scene name='pdbligand=OHX:OSMIUM+(III)+HEXAMMINE'>OHX</scene>, <scene name='pdbligand=ZBA:12,13-EPOXYTRICHOTHEC-9-ENE-3,4,8,15-TETROL-4,15-DIACETATE-8-ISOVALERATE'>ZBA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4uju|4uju]], [[4ujv|4ujv]], [[4ujw|4ujw]], [[4ujx|4ujx]], [[4ujy|4ujy]]</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=4u6f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u6f OCA], [https://pdbe.org/4u6f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4u6f RCSB], [https://www.ebi.ac.uk/pdbsum/4u6f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4u6f ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4u6f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u6f OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4u6f RCSB], [http://www.ebi.ac.uk/pdbsum/4u6f PDBsum]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/RS27A_YEAST RS27A_YEAST]] Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, and DNA-damage responses. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling (By similarity).  40S ribosomal protein S31 is a component of the 40S subunit of the ribosome (By similarity). [[http://www.uniprot.org/uniprot/RS19A_YEAST RS19A_YEAST]] Required for proper maturation of the small (40S) ribosomal subunit. Binds to 40s pre-ribosomal particles, probably required after association of NOC4 but before association of ENP1, TSR1 and RIO2 with 20/21S pre-rRNA.<ref>PMID:16159874</ref> <ref>PMID:17726054</ref>  [[http://www.uniprot.org/uniprot/RS14A_YEAST RS14A_YEAST]] Involved in nucleolar processing of pre-18S ribosomal RNA and ribosome assembly.<ref>PMID:15590835</ref>  [[http://www.uniprot.org/uniprot/RL25_YEAST RL25_YEAST]] This protein binds to a specific region on the 26S rRNA. [[http://www.uniprot.org/uniprot/RS18A_YEAST RS18A_YEAST]] Located at the top of the head of the 40S subunit, it contacts several helices of the 18S rRNA (By similarity).[HAMAP-Rule:MF_01315] [[http://www.uniprot.org/uniprot/STM1_YEAST STM1_YEAST]] Binds specifically G4 quadruplex (these are four-stranded right-handed helices, stabilized by guanine base quartets) and purine motif triplex (characterized by a third, antiparallel purine-rich DNA strand located within the major groove of a homopurine stretch of duplex DNA) nucleic acid structures. These structures may be present at telomeres or in rRNAs. Acts with CDC13 to control telomere length homeostasis. Involved in the control of the apoptosis-like cell death.<ref>PMID:15044472</ref>  [[http://www.uniprot.org/uniprot/RS9A_YEAST RS9A_YEAST]] Involved in nucleolar processing of pre-18S ribosomal RNA and ribosome assembly.<ref>PMID:15590835</ref>  [[http://www.uniprot.org/uniprot/RL11B_YEAST RL11B_YEAST]] Binds to 5S ribosomal RNA. [[http://www.uniprot.org/uniprot/RL4A_YEAST RL4A_YEAST]] Participates in the regulation of the accumulation of its own mRNA.<ref>PMID:2065661</ref>  [[http://www.uniprot.org/uniprot/RLA0_YEAST RLA0_YEAST]] Ribosomal protein P0 is the functional equivalent of E.coli protein L10. [[http://www.uniprot.org/uniprot/RL37A_YEAST RL37A_YEAST]] Binds to the 23S rRNA (By similarity). [[http://www.uniprot.org/uniprot/RL401_YEAST RL401_YEAST]] Ubiquitin: exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, and DNA-damage responses. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling (By similarity).<ref>PMID:23169626</ref>  60S ribosomal protein L40: component of the 60S subunit of the ribosome. Ribosomal protein L40 is essential for translation of a subset of cellular transcripts, including stress response transcripts, such as DDR2.<ref>PMID:23169626</ref>  [[http://www.uniprot.org/uniprot/RS15_YEAST RS15_YEAST]] Involved in the nuclear export of the small ribosomal subunit. Has a role in the late stage of the assembly of pre-40S particles within the nucleus and controls their export to the cytoplasm.<ref>PMID:15167894</ref>  [[http://www.uniprot.org/uniprot/RSSA1_YEAST RSSA1_YEAST]] Required for the assembly and/or stability of the 40S ribosomal subunit. Required for the processing of the 20S rRNA-precursor to mature 18S rRNA in a late step of the maturation of 40S ribosomal subunits.<ref>PMID:9973221</ref> <ref>PMID:14627813</ref> [[http://www.uniprot.org/uniprot/RL5_YEAST RL5_YEAST]] Binds 5S RNA and is required for 60S subunit assembly. [[http://www.uniprot.org/uniprot/RS21A_YEAST RS21A_YEAST]] Required for the processing of the 20S rRNA-precursor to mature 18S rRNA in a late step of the maturation of 40S ribosomal subunits. Has a physiological role leading to 18S rRNA stability.<ref>PMID:14627813</ref>  [[http://www.uniprot.org/uniprot/RS7A_YEAST RS7A_YEAST]] Involved in nucleolar processing of pre-18S ribosomal RNA and ribosome assembly.<ref>PMID:15590835</ref>  [[http://www.uniprot.org/uniprot/RS6A_YEAST RS6A_YEAST]] Involved in nucleolar processing of pre-18S ribosomal RNA and ribosome assembly.<ref>PMID:15590835</ref>  [[http://www.uniprot.org/uniprot/RS2_YEAST RS2_YEAST]] Important in the assembly and function of the 40S ribosomal subunit. Mutations in this protein affects the control of translational fidelity. Involved in nucleolar processing of pre-18S ribosomal RNA and ribosome assembly.<ref>PMID:15590835</ref>  [[http://www.uniprot.org/uniprot/GBLP_YEAST GBLP_YEAST]] Located at the head of the 40S ribosomal subunit in the vicinity of the mRNA exit channel, it serves as a scaffold protein that can recruit other proteins to the ribosome. Involved in the negative regulation of translation of a specific subset of proteins.<ref>PMID:15340087</ref> 
[https://www.uniprot.org/uniprot/RSSA1_YEAST RSSA1_YEAST] Required for the assembly and/or stability of the 40S ribosomal subunit. Required for the processing of the 20S rRNA-precursor to mature 18S rRNA in a late step of the maturation of 40S ribosomal subunits.<ref>PMID:9973221</ref> <ref>PMID:14627813</ref>  
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
</div>
<div class="pdbe-citations 4u6f" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Ribosome 3D structures|Ribosome 3D structures]]
*[[Ribosome 3D structures|Ribosome 3D structures]]
*[[3D sructureseceptor for activated protein kinase C 1|3D sructureseceptor for activated protein kinase C 1]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Saccharomyces cerevisiae atcc 204508 / s288c]]
[[Category: Large Structures]]
[[Category: Loubresse, N Garreau de]]
[[Category: Saccharomyces cerevisiae S288C]]
[[Category: Prokhorova, I]]
[[Category: Garreau de Loubresse N]]
[[Category: Yusupov, M]]
[[Category: Prokhorova I]]
[[Category: Yusupova, G]]
[[Category: Yusupov M]]
[[Category: Antibiotic]]
[[Category: Yusupova G]]
[[Category: Eukaryote]]
[[Category: Inhibitor]]
[[Category: Ribosome]]
[[Category: Rna-protein complex]]
[[Category: Translation]]

Latest revision as of 15:27, 20 December 2023

Crystal structure of T-2 toxin bound to the yeast 80S ribosomeCrystal structure of T-2 toxin bound to the yeast 80S ribosome

Structural highlights

4u6f is a 20 chain structure with sequence from Saccharomyces cerevisiae S288C. This structure supersedes the now removed PDB entries 4uju, 4ujv, 4ujw, 4ujx and 4ujy. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3.1Å
Ligands:, , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RSSA1_YEAST Required for the assembly and/or stability of the 40S ribosomal subunit. Required for the processing of the 20S rRNA-precursor to mature 18S rRNA in a late step of the maturation of 40S ribosomal subunits.[1] [2]

Publication Abstract from PubMed

The ribosome is a molecular machine responsible for protein synthesis and a major target for small-molecule inhibitors. Compared to the wealth of structural information available on ribosome-targeting antibiotics in bacteria, our understanding of the binding mode of ribosome inhibitors in eukaryotes is currently limited. Here we used X-ray crystallography to determine 16 high-resolution structures of 80S ribosomes from Saccharomyces cerevisiae in complexes with 12 eukaryote-specific and 4 broad-spectrum inhibitors. All inhibitors were found associated with messenger RNA and transfer RNA binding sites. In combination with kinetic experiments, the structures suggest a model for the action of cycloheximide and lactimidomycin, which explains why lactimidomycin, the larger compound, specifically targets the first elongation cycle. The study defines common principles of targeting and resistance, provides insights into translation inhibitor mode of action and reveals the structural determinants responsible for species selectivity which could guide future drug development.

Structural basis for the inhibition of the eukaryotic ribosome.,Garreau de Loubresse N, Prokhorova I, Holtkamp W, Rodnina MV, Yusupova G, Yusupov M Nature. 2014 Sep 25;513(7519):517-22. doi: 10.1038/nature13737. Epub 2014 Sep 10. PMID:25209664[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Ford CL, Randal-Whitis L, Ellis SR. Yeast proteins related to the p40/laminin receptor precursor are required for 20S ribosomal RNA processing and the maturation of 40S ribosomal subunits. Cancer Res. 1999 Feb 1;59(3):704-10. PMID:9973221
  2. ↑ Tabb-Massey A, Caffrey JM, Logsden P, Taylor S, Trent JO, Ellis SR. Ribosomal proteins Rps0 and Rps21 of Saccharomyces cerevisiae have overlapping functions in the maturation of the 3' end of 18S rRNA. Nucleic Acids Res. 2003 Dec 1;31(23):6798-805. PMID:14627813
  3. ↑ Garreau de Loubresse N, Prokhorova I, Holtkamp W, Rodnina MV, Yusupova G, Yusupov M. Structural basis for the inhibition of the eukaryotic ribosome. Nature. 2014 Sep 25;513(7519):517-22. doi: 10.1038/nature13737. Epub 2014 Sep 10. PMID:25209664 doi:http://dx.doi.org/10.1038/nature13737

4u6f, resolution 3.10Å

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