6lkq

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==The Structural Basis for Inhibition of Ribosomal Translocation by Viomycin==
==The Structural Basis for Inhibition of Ribosomal Translocation by Viomycin==
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<StructureSection load='6lkq' size='340' side='right'caption='[[6lkq]]' scene=''>
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<StructureSection load='6lkq' size='340' side='right'caption='[[6lkq]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LKQ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6LKQ FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6lkq]] is a 62 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LKQ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6LKQ FirstGlance]. <br>
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</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6lkq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lkq OCA], [http://pdbe.org/6lkq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6lkq RCSB], [http://www.ebi.ac.uk/pdbsum/6lkq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6lkq ProSAT]</span></td></tr>
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</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=5OH:(2S)-AMINO[(4R,6S)-2-AMINO-6-HYDROXY-3,4,5,6-TETRAHYDROPYRIMIDIN-4-YL]ETHANOIC+ACID'>5OH</scene>, <scene name='pdbligand=DPP:DIAMINOPROPANOIC+ACID'>DPP</scene>, <scene name='pdbligand=KBE:BETA-LYSINE'>KBE</scene>, <scene name='pdbligand=UAL:(2Z)-2-AMINO-3-(CARBAMOYLAMINO)PROP-2-ENOIC+ACID'>UAL</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6lkq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lkq OCA], [http://pdbe.org/6lkq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6lkq RCSB], [http://www.ebi.ac.uk/pdbsum/6lkq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6lkq ProSAT]</span></td></tr>
</table>
</table>
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== Function ==
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[[http://www.uniprot.org/uniprot/H4JDL8_ECOLX H4JDL8_ECOLX]] This is one of the proteins that binds and probably mediates the attachment of the 5S RNA into the large ribosomal subunit, where it forms part of the central protuberance.[HAMAP-Rule:MF_01337] [[http://www.uniprot.org/uniprot/A0A1X3LPI5_ECOLX A0A1X3LPI5_ECOLX]] One of the primary rRNA binding proteins. Required for association of the 30S and 50S subunits to form the 70S ribosome, for tRNA binding and peptide bond formation. It has been suggested to have peptidyltransferase activity; this is somewhat controversial. Makes several contacts with the 16S rRNA in the 70S ribosome.[HAMAP-Rule:MF_01320] [[http://www.uniprot.org/uniprot/U9ZUM7_ECOLX U9ZUM7_ECOLX]] One of the primary rRNA binding proteins, it binds directly to 16S rRNA central domain where it helps coordinate assembly of the platform of the 30S subunit.[HAMAP-Rule:MF_01302] [[http://www.uniprot.org/uniprot/H4J053_ECOLX H4J053_ECOLX]] Forms part of the ribosomal stalk which helps the ribosome interact with GTP-bound translation factors.[HAMAP-Rule:MF_00736][RuleBase:RU003979][SAAS:SAAS00731150] [[http://www.uniprot.org/uniprot/E9TDX6_ECOLX E9TDX6_ECOLX]] Binds as a heterodimer with protein S6 to the central domain of the 16S rRNA, where it helps stabilize the platform of the 30S subunit.[HAMAP-Rule:MF_00270] [[http://www.uniprot.org/uniprot/A0A376HTV6_ECOLX A0A376HTV6_ECOLX]] Binds the lower part of the 30S subunit head. Binds mRNA in the 70S ribosome, positioning it for translation.[HAMAP-Rule:MF_01309] [[http://www.uniprot.org/uniprot/S1EA57_ECOLX S1EA57_ECOLX]] Protein S19 forms a complex with S13 that binds strongly to the 16S ribosomal RNA.[HAMAP-Rule:MF_00531] [[http://www.uniprot.org/uniprot/H4LI23_ECOLX H4LI23_ECOLX]] Binds 23S rRNA and is also seen to make contacts with the A and possibly P site tRNAs.[HAMAP-Rule:MF_01342][RuleBase:RU004414] [[http://www.uniprot.org/uniprot/T6LV72_ECOLX T6LV72_ECOLX]] One of the primary rRNA binding proteins, it binds specifically to the 5'-end of 16S ribosomal RNA.[HAMAP-Rule:MF_01345] [[http://www.uniprot.org/uniprot/S1EW51_ECOLX S1EW51_ECOLX]] This protein is one of the early assembly proteins of the 50S ribosomal subunit, although it is not seen to bind rRNA by itself. It is important during the early stages of 50S assembly.[HAMAP-Rule:MF_01366][RuleBase:RU003878][SAAS:SAAS00725369] [[http://www.uniprot.org/uniprot/V0AIU3_ECOLX V0AIU3_ECOLX]] This protein binds to the 23S rRNA, and is important in its secondary structure. It is located near the subunit interface in the base of the L7/L12 stalk, and near the tRNA binding site of the peptidyltransferase center.[HAMAP-Rule:MF_01365][RuleBase:RU003870] [[http://www.uniprot.org/uniprot/V0YSM1_ECOLX V0YSM1_ECOLX]] Binds to 23S rRNA. Forms part of two intersubunit bridges in the 70S ribosome.[HAMAP-Rule:MF_01367][RuleBase:RU003950] [[http://www.uniprot.org/uniprot/A0A029IK47_ECOLX A0A029IK47_ECOLX]] Forms an intersubunit bridge (bridge B4) with the 23S rRNA of the 50S subunit in the ribosome.[HAMAP-Rule:MF_01343] One of the primary rRNA binding proteins, it binds directly to 16S rRNA where it helps nucleate assembly of the platform of the 30S subunit by binding and bridging several RNA helices of the 16S rRNA.[HAMAP-Rule:MF_01343][RuleBase:RU004524] [[http://www.uniprot.org/uniprot/A0A1X3LA41_ECOLX A0A1X3LA41_ECOLX]] Forms part of the ribosomal stalk, playing a central role in the interaction of the ribosome with GTP-bound translation factors.[HAMAP-Rule:MF_00362][SAAS:SAAS01154773] [[http://www.uniprot.org/uniprot/H4IXW7_ECOLX H4IXW7_ECOLX]] This is 1 of the proteins that binds and probably mediates the attachment of the 5S RNA into the large ribosomal subunit, where it forms part of the central protuberance. In the 70S ribosome it contacts protein S13 of the 30S subunit (bridge B1b), connecting the 2 subunits; this bridge is implicated in subunit movement. Contacts the P site tRNA; the 5S rRNA and some of its associated proteins might help stabilize positioning of ribosome-bound tRNAs.[HAMAP-Rule:MF_01333] [[http://www.uniprot.org/uniprot/A0A4P8B3R1_ECO57 A0A4P8B3R1_ECO57]] Located on the platform of the 30S subunit, it bridges several disparate RNA helices of the 16S rRNA. Forms part of the Shine-Dalgarno cleft in the 70S ribosome.[HAMAP-Rule:MF_01310] [[http://www.uniprot.org/uniprot/L4V445_ECOLX L4V445_ECOLX]] This protein binds to 23S rRNA in the presence of protein L20.[HAMAP-Rule:MF_01363][RuleBase:RU000562][SAAS:SAAS00352917] [[http://www.uniprot.org/uniprot/L3C3P4_ECOLX L3C3P4_ECOLX]] Interacts with and stabilizes bases of the 16S rRNA that are involved in tRNA selection in the A site and with the mRNA backbone. Located at the interface of the 30S and 50S subunits, it traverses the body of the 30S subunit contacting proteins on the other side and probably holding the rRNA structure together. The combined cluster of proteins S8, S12 and S17 appears to hold together the shoulder and platform of the 30S subunit.[HAMAP-Rule:MF_00403][RuleBase:RU003623] With S4 and S5 plays an important role in translational accuracy.[HAMAP-Rule:MF_00403][RuleBase:RU003623] [[http://www.uniprot.org/uniprot/I2X6U5_ECOLX I2X6U5_ECOLX]] One of the primary rRNA binding proteins, it binds directly near the 3'-end of the 23S rRNA, where it nucleates assembly of the 50S subunit.[HAMAP-Rule:MF_01325][RuleBase:RU003906] [[http://www.uniprot.org/uniprot/A0A090BZT4_ECOLX A0A090BZT4_ECOLX]] Binds 16S rRNA, required for the assembly of 30S particles and may also be responsible for determining the conformation of the 16S rRNA at the A site.[HAMAP-Rule:MF_00537] [[http://www.uniprot.org/uniprot/L3C159_ECOLX L3C159_ECOLX]] Forms part of the polypeptide exit tunnel.[HAMAP-Rule:MF_01328] One of the primary rRNA binding proteins, this protein initially binds near the 5'-end of the 23S rRNA. It is important during the early stages of 50S assembly. It makes multiple contacts with different domains of the 23S rRNA in the assembled 50S subunit and ribosome.[HAMAP-Rule:MF_01328] [[http://www.uniprot.org/uniprot/A0A037Y8L6_ECOLX A0A037Y8L6_ECOLX]] Binds to the 23S rRNA.[HAMAP-Rule:MF_01341][SAAS:SAAS00124822] [[http://www.uniprot.org/uniprot/D6I218_ECOLX D6I218_ECOLX]] One of the primary rRNA binding proteins, it binds directly to 16S rRNA where it nucleates assembly of the head domain of the 30S subunit. Is located at the subunit interface close to the decoding center, probably blocks exit of the E-site tRNA.[HAMAP-Rule:MF_00480] [[http://www.uniprot.org/uniprot/A0A4C9D1M4_ECOLX A0A4C9D1M4_ECOLX]] Forms part of the ribosomal stalk which helps the ribosome interact with GTP-bound translation factors. Is thus essential for accurate translation.[HAMAP-Rule:MF_00368] [[http://www.uniprot.org/uniprot/D7Y4U5_ECOLX D7Y4U5_ECOLX]] This is one of the proteins that binds to the 5S RNA in the ribosome where it forms part of the central protuberance.[HAMAP-Rule:MF_01336][SAAS:SAAS01080239] [[http://www.uniprot.org/uniprot/F4TL38_ECOLX F4TL38_ECOLX]] The globular domain of the protein is located near the polypeptide exit tunnel on the outside of the subunit, while an extended beta-hairpin is found that lines the wall of the exit tunnel in the center of the 70S ribosome.[HAMAP-Rule:MF_01331] This protein binds specifically to 23S rRNA; its binding is stimulated by other ribosomal proteins, e.g., L4, L17, and L20. It is important during the early stages of 50S assembly. It makes multiple contacts with different domains of the 23S rRNA in the assembled 50S subunit and ribosome.[HAMAP-Rule:MF_01331][RuleBase:RU004008] [[http://www.uniprot.org/uniprot/A0A4P8BV83_ECOLX A0A4P8BV83_ECOLX]] One of the primary rRNA binding proteins, it binds directly to 16S rRNA where it nucleates assembly of the body of the 30S subunit.[HAMAP-Rule:MF_01306] With S5 and S12 plays an important role in translational accuracy.[HAMAP-Rule:MF_01306] [[http://www.uniprot.org/uniprot/A0A5B9AU26_ECOLX A0A5B9AU26_ECOLX]] Involved in the binding of tRNA to the ribosomes.[HAMAP-Rule:MF_00508] [[http://www.uniprot.org/uniprot/A0A069XLE9_ECOLX A0A069XLE9_ECOLX]] Located at the top of the head of the 30S subunit, it contacts several helices of the 16S rRNA. In the 70S ribosome it contacts the 23S rRNA (bridge B1a) and protein L5 of the 50S subunit (bridge B1b), connecting the 2 subunits; these bridges are implicated in subunit movement. Contacts the tRNAs in the A and P-sites.[HAMAP-Rule:MF_01315] [[http://www.uniprot.org/uniprot/F4TL32_ECOLX F4TL32_ECOLX]] One of the proteins that surrounds the polypeptide exit tunnel on the outside of the subunit.[HAMAP-Rule:MF_01326] One of two assembly initiator proteins, it binds directly to the 5'-end of the 23S rRNA, where it nucleates assembly of the 50S subunit.[HAMAP-Rule:MF_01326] [[http://www.uniprot.org/uniprot/F4SQ30_ECOLX F4SQ30_ECOLX]] Located at the back of the 30S subunit body where it stabilizes the conformation of the head with respect to the body.[HAMAP-Rule:MF_01307][SAAS:SAAS00085417] With S4 and S12 plays an important role in translational accuracy.[HAMAP-Rule:MF_01307][SAAS:SAAS00085429] [[http://www.uniprot.org/uniprot/V6FS92_ECOLX V6FS92_ECOLX]] Binds directly to 23S ribosomal RNA and is necessary for the in vitro assembly process of the 50S ribosomal subunit. It is not involved in the protein synthesizing functions of that subunit.[HAMAP-Rule:MF_00382][RuleBase:RU000560] [[http://www.uniprot.org/uniprot/S1EUY1_ECOLX S1EUY1_ECOLX]] One of the early assembly proteins it binds 23S rRNA. One of the proteins that surrounds the polypeptide exit tunnel on the outside of the ribosome. Forms the main docking site for trigger factor binding to the ribosome.[HAMAP-Rule:MF_01369] [[http://www.uniprot.org/uniprot/D7ZAS2_ECOLX D7ZAS2_ECOLX]] Binds directly to 16S ribosomal RNA.[HAMAP-Rule:MF_00500] [[http://www.uniprot.org/uniprot/C3SE77_ECOLX C3SE77_ECOLX]] Increases the formation of ribosomal termination complexes and stimulates activities of RF-1 and RF-2. It binds guanine nucleotides and has strong preference for UGA stop codons. It may interact directly with the ribosome. The stimulation of RF-1 and RF-2 is significantly reduced by GTP and GDP, but not by GMP.[HAMAP-Rule:MF_00072][SAAS:SAAS01159260] [[http://www.uniprot.org/uniprot/A0A3L2GT12_ECOLX A0A3L2GT12_ECOLX]] Binds together with S18 to 16S ribosomal RNA.[HAMAP-Rule:MF_00360][SAAS:SAAS00348112]
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Viomycin, an antibiotic that has been used to fight tuberculosis infections, is believed to block the translocation step of protein synthesis by inhibiting ribosomal subunit dissociation and trapping the ribosome in an intermediate state of intersubunit rotation. The mechanism by which viomycin stabilizes this state remains unexplained. To address this, we have determined cryo-EM and X-ray crystal structures of Escherichia coli 70S ribosome complexes trapped in a rotated state by viomycin. The 3.8-A resolution cryo-EM structure reveals a ribosome trapped in the hybrid state with 8.6 degrees intersubunit rotation and 5.3 degrees rotation of the 30S subunit head domain, bearing a single P/E state transfer RNA (tRNA). We identify five different binding sites for viomycin, four of which have not been previously described. To resolve the details of their binding interactions, we solved the 3.1-A crystal structure of a viomycin-bound ribosome complex, revealing that all five viomycins bind to ribosomal RNA. One of these (Vio1) corresponds to the single viomycin that was previously identified in a complex with a nonrotated classical-state ribosome. Three of the newly observed binding sites (Vio3, Vio4, and Vio5) are clustered at intersubunit bridges, consistent with the ability of viomycin to inhibit subunit dissociation. We propose that one or more of these same three viomycins induce intersubunit rotation by selectively binding the rotated state of the ribosome at dynamic elements of 16S and 23S rRNA, thus, blocking conformational changes associated with molecular movements that are required for translocation.
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The structural basis for inhibition of ribosomal translocation by viomycin.,Zhang L, Wang YH, Zhang X, Lancaster L, Zhou J, Noller HF Proc Natl Acad Sci U S A. 2020 Apr 27. pii: 2002888117. doi:, 10.1073/pnas.2002888117. PMID:32341159<ref>PMID:32341159</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 6lkq" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Escherichia coli]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Lancaster L]]
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[[Category: Lancaster, L]]
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[[Category: Noller HF]]
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[[Category: Noller, H F]]
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[[Category: Wang YH]]
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[[Category: Wang, Y H]]
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[[Category: Zhang L]]
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[[Category: Zhang, L]]
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[[Category: Zhou J]]
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[[Category: Zhou, J]]
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[[Category: 70s ribosome viomycin translocation]]
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[[Category: Translation]]

Revision as of 05:49, 13 May 2020

The Structural Basis for Inhibition of Ribosomal Translocation by Viomycin

PDB ID 6lkq

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