5ju8: Difference between revisions

Latest revision as of 05:13, 24 June 2026

Cryo-EM structure of an ErmBL-stalled ribosome in complex with P-, and E-tRNA

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Structural highlights

5ju8 is a 10 chain structure with sequence from Escherichia coli K-12. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.6Å
Ligands:	2MA, 4SU, 5MU, 6MZ, 7MG, CM0, ERY, H2U, PSU, QUO
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RS4_ECOLI One of two assembly initiator proteins for the 30S subunit, it binds directly to 16S rRNA where it nucleates assembly of the body of the 30S subunit.^[1] ^[2] ^[3] With S5 and S12 plays an important role in translational accuracy; many suppressors of streptomycin-dependent mutants of protein S12 are found in this protein, some but not all of which decrease translational accuracy (ram, ribosomal ambiguity mutations).^[4] ^[5] ^[6] Plays a role in mRNA unwinding by the ribosome, possibly by forming part of a processivity clamp.^[7] ^[8] ^[9] Protein S4 is also a translational repressor protein, it controls the translation of the alpha-operon (which codes for S13, S11, S4, RNA polymerase alpha subunit, and L17) by binding to its mRNA.^[10] ^[11] ^[12] Also functions as a rho-dependent antiterminator of rRNA transcription, increasing the synthesis of rRNA under conditions of excess protein, allowing a more rapid return to homeostasis. Binds directly to RNA polymerase.^[13] ^[14] ^[15]

Publication Abstract from PubMed

Nascent polypeptides can induce ribosome stalling, regulating downstream genes. Stalling of ErmBL peptide translation in the presence of the macrolide antibiotic erythromycin leads to resistance in Streptococcus sanguis. To reveal this stalling mechanism we obtained 3.6-A-resolution cryo-EM structures of ErmBL-stalled ribosomes with erythromycin. The nascent peptide adopts an unusual conformation with the C-terminal Asp10 side chain in a previously unseen rotated position. Together with molecular dynamics simulations, the structures indicate that peptide-bond formation is inhibited by displacement of the peptidyl-tRNA A76 ribose from its canonical position, and by non-productive interactions of the A-tRNA Lys11 side chain with the A-site crevice. These two effects combine to perturb peptide-bond formation by increasing the distance between the attacking Lys11 amine and the Asp10 carbonyl carbon. The interplay between drug, peptide and ribosome uncovered here also provides insight into the fundamental mechanism of peptide-bond formation.

A combined cryo-EM and molecular dynamics approach reveals the mechanism of ErmBL-mediated translation arrest.,Arenz S, Bock LV, Graf M, Innis CA, Beckmann R, Grubmuller H, Vaiana AC, Wilson DN Nat Commun. 2016 Jul 6;7:12026. doi: 10.1038/ncomms12026. PMID:27380950^[16]

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

References

↑ Nowotny V, Nierhaus KH. Assembly of the 30S subunit from Escherichia coli ribosomes occurs via two assembly domains which are initiated by S4 and S7. Biochemistry. 1988 Sep 6;27(18):7051-5. PMID:2461734
↑ Torres M, Condon C, Balada JM, Squires C, Squires CL. Ribosomal protein S4 is a transcription factor with properties remarkably similar to NusA, a protein involved in both non-ribosomal and ribosomal RNA antitermination. EMBO J. 2001 Jul 16;20(14):3811-20. PMID:11447122 doi:10.1093/emboj/20.14.3811
↑ Takyar S, Hickerson RP, Noller HF. mRNA helicase activity of the ribosome. Cell. 2005 Jan 14;120(1):49-58. PMID:15652481 doi:10.1016/j.cell.2004.11.042
↑ Nowotny V, Nierhaus KH. Assembly of the 30S subunit from Escherichia coli ribosomes occurs via two assembly domains which are initiated by S4 and S7. Biochemistry. 1988 Sep 6;27(18):7051-5. PMID:2461734
↑ Torres M, Condon C, Balada JM, Squires C, Squires CL. Ribosomal protein S4 is a transcription factor with properties remarkably similar to NusA, a protein involved in both non-ribosomal and ribosomal RNA antitermination. EMBO J. 2001 Jul 16;20(14):3811-20. PMID:11447122 doi:10.1093/emboj/20.14.3811
↑ Takyar S, Hickerson RP, Noller HF. mRNA helicase activity of the ribosome. Cell. 2005 Jan 14;120(1):49-58. PMID:15652481 doi:10.1016/j.cell.2004.11.042
↑ Nowotny V, Nierhaus KH. Assembly of the 30S subunit from Escherichia coli ribosomes occurs via two assembly domains which are initiated by S4 and S7. Biochemistry. 1988 Sep 6;27(18):7051-5. PMID:2461734
↑ Torres M, Condon C, Balada JM, Squires C, Squires CL. Ribosomal protein S4 is a transcription factor with properties remarkably similar to NusA, a protein involved in both non-ribosomal and ribosomal RNA antitermination. EMBO J. 2001 Jul 16;20(14):3811-20. PMID:11447122 doi:10.1093/emboj/20.14.3811
↑ Takyar S, Hickerson RP, Noller HF. mRNA helicase activity of the ribosome. Cell. 2005 Jan 14;120(1):49-58. PMID:15652481 doi:10.1016/j.cell.2004.11.042
↑ Nowotny V, Nierhaus KH. Assembly of the 30S subunit from Escherichia coli ribosomes occurs via two assembly domains which are initiated by S4 and S7. Biochemistry. 1988 Sep 6;27(18):7051-5. PMID:2461734
↑ Torres M, Condon C, Balada JM, Squires C, Squires CL. Ribosomal protein S4 is a transcription factor with properties remarkably similar to NusA, a protein involved in both non-ribosomal and ribosomal RNA antitermination. EMBO J. 2001 Jul 16;20(14):3811-20. PMID:11447122 doi:10.1093/emboj/20.14.3811
↑ Takyar S, Hickerson RP, Noller HF. mRNA helicase activity of the ribosome. Cell. 2005 Jan 14;120(1):49-58. PMID:15652481 doi:10.1016/j.cell.2004.11.042
↑ Nowotny V, Nierhaus KH. Assembly of the 30S subunit from Escherichia coli ribosomes occurs via two assembly domains which are initiated by S4 and S7. Biochemistry. 1988 Sep 6;27(18):7051-5. PMID:2461734
↑ Torres M, Condon C, Balada JM, Squires C, Squires CL. Ribosomal protein S4 is a transcription factor with properties remarkably similar to NusA, a protein involved in both non-ribosomal and ribosomal RNA antitermination. EMBO J. 2001 Jul 16;20(14):3811-20. PMID:11447122 doi:10.1093/emboj/20.14.3811
↑ Takyar S, Hickerson RP, Noller HF. mRNA helicase activity of the ribosome. Cell. 2005 Jan 14;120(1):49-58. PMID:15652481 doi:10.1016/j.cell.2004.11.042
↑ Arenz S, Bock LV, Graf M, Innis CA, Beckmann R, Grubmuller H, Vaiana AC, Wilson DN. A combined cryo-EM and molecular dynamics approach reveals the mechanism of ErmBL-mediated translation arrest. Nat Commun. 2016 Jul 6;7:12026. doi: 10.1038/ncomms12026. PMID:27380950 doi:https://dx.doi.org/10.1038/ncomms12026

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OCA

[1] Nowotny V, Nierhaus KH. Assembly of the 30S subunit from Escherichia coli ribosomes occurs via two assembly domains which are initiated by S4 and S7. Biochemistry. 1988 Sep 6;27(18):7051-5. PMID:2461734

[2] Torres M, Condon C, Balada JM, Squires C, Squires CL. Ribosomal protein S4 is a transcription factor with properties remarkably similar to NusA, a protein involved in both non-ribosomal and ribosomal RNA antitermination. EMBO J. 2001 Jul 16;20(14):3811-20. PMID:11447122 doi:10.1093/emboj/20.14.3811

[3] Takyar S, Hickerson RP, Noller HF. mRNA helicase activity of the ribosome. Cell. 2005 Jan 14;120(1):49-58. PMID:15652481 doi:10.1016/j.cell.2004.11.042

[4] Nowotny V, Nierhaus KH. Assembly of the 30S subunit from Escherichia coli ribosomes occurs via two assembly domains which are initiated by S4 and S7. Biochemistry. 1988 Sep 6;27(18):7051-5. PMID:2461734

[5] Torres M, Condon C, Balada JM, Squires C, Squires CL. Ribosomal protein S4 is a transcription factor with properties remarkably similar to NusA, a protein involved in both non-ribosomal and ribosomal RNA antitermination. EMBO J. 2001 Jul 16;20(14):3811-20. PMID:11447122 doi:10.1093/emboj/20.14.3811

[6] Takyar S, Hickerson RP, Noller HF. mRNA helicase activity of the ribosome. Cell. 2005 Jan 14;120(1):49-58. PMID:15652481 doi:10.1016/j.cell.2004.11.042

[7] Nowotny V, Nierhaus KH. Assembly of the 30S subunit from Escherichia coli ribosomes occurs via two assembly domains which are initiated by S4 and S7. Biochemistry. 1988 Sep 6;27(18):7051-5. PMID:2461734

[8] Torres M, Condon C, Balada JM, Squires C, Squires CL. Ribosomal protein S4 is a transcription factor with properties remarkably similar to NusA, a protein involved in both non-ribosomal and ribosomal RNA antitermination. EMBO J. 2001 Jul 16;20(14):3811-20. PMID:11447122 doi:10.1093/emboj/20.14.3811

[9] Takyar S, Hickerson RP, Noller HF. mRNA helicase activity of the ribosome. Cell. 2005 Jan 14;120(1):49-58. PMID:15652481 doi:10.1016/j.cell.2004.11.042

[10] Nowotny V, Nierhaus KH. Assembly of the 30S subunit from Escherichia coli ribosomes occurs via two assembly domains which are initiated by S4 and S7. Biochemistry. 1988 Sep 6;27(18):7051-5. PMID:2461734

[11] Torres M, Condon C, Balada JM, Squires C, Squires CL. Ribosomal protein S4 is a transcription factor with properties remarkably similar to NusA, a protein involved in both non-ribosomal and ribosomal RNA antitermination. EMBO J. 2001 Jul 16;20(14):3811-20. PMID:11447122 doi:10.1093/emboj/20.14.3811

[12] Takyar S, Hickerson RP, Noller HF. mRNA helicase activity of the ribosome. Cell. 2005 Jan 14;120(1):49-58. PMID:15652481 doi:10.1016/j.cell.2004.11.042

[13] Nowotny V, Nierhaus KH. Assembly of the 30S subunit from Escherichia coli ribosomes occurs via two assembly domains which are initiated by S4 and S7. Biochemistry. 1988 Sep 6;27(18):7051-5. PMID:2461734

[14] Torres M, Condon C, Balada JM, Squires C, Squires CL. Ribosomal protein S4 is a transcription factor with properties remarkably similar to NusA, a protein involved in both non-ribosomal and ribosomal RNA antitermination. EMBO J. 2001 Jul 16;20(14):3811-20. PMID:11447122 doi:10.1093/emboj/20.14.3811

[15] Takyar S, Hickerson RP, Noller HF. mRNA helicase activity of the ribosome. Cell. 2005 Jan 14;120(1):49-58. PMID:15652481 doi:10.1016/j.cell.2004.11.042

[16] Arenz S, Bock LV, Graf M, Innis CA, Beckmann R, Grubmuller H, Vaiana AC, Wilson DN. A combined cryo-EM and molecular dynamics approach reveals the mechanism of ErmBL-mediated translation arrest. Nat Commun. 2016 Jul 6;7:12026. doi: 10.1038/ncomms12026. PMID:27380950 doi:https://dx.doi.org/10.1038/ncomms12026

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5ju8 is ON HOLD
+==Cryo-EM structure of an ErmBL-stalled ribosome in complex with P-, and E-tRNA==
+<SX load='5ju8' size='340' side='right' viewer='molstar' caption='[[5ju8]], [[Resolution|resolution]] 3.60&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5ju8]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JU8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JU8 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]] 3.6&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2MA:2-METHYLADENOSINE-5-MONOPHOSPHATE'>2MA</scene>, <scene name='pdbligand=4SU:4-THIOURIDINE-5-MONOPHOSPHATE'>4SU</scene>, <scene name='pdbligand=5MU:5-METHYLURIDINE+5-MONOPHOSPHATE'>5MU</scene>, <scene name='pdbligand=6MZ:N6-METHYLADENOSINE-5-MONOPHOSPHATE'>6MZ</scene>, <scene name='pdbligand=7MG:7N-METHYL-8-HYDROGUANOSINE-5-MONOPHOSPHATE'>7MG</scene>, <scene name='pdbligand=CM0:5-(CARBOXYMETHOXY)+URIDINE-5-MONOPHOSPHATE'>CM0</scene>, <scene name='pdbligand=ERY:ERYTHROMYCIN+A'>ERY</scene>, <scene name='pdbligand=H2U:5,6-DIHYDROURIDINE-5-MONOPHOSPHATE'>H2U</scene>, <scene name='pdbligand=PSU:PSEUDOURIDINE-5-MONOPHOSPHATE'>PSU</scene>, <scene name='pdbligand=QUO:2-AMINO-7-DEAZA-(2,3-DIHYDROXY-CYCLOPENTYLAMINO)-GUANOSINE-5-MONOPHOSPHATE'>QUO</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=5ju8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ju8 OCA], [https://pdbe.org/5ju8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ju8 RCSB], [https://www.ebi.ac.uk/pdbsum/5ju8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ju8 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/RS4_ECOLI RS4_ECOLI] One of two assembly initiator proteins for the 30S subunit, it binds directly to 16S rRNA where it nucleates assembly of the body of the 30S subunit.<ref>PMID:2461734</ref> <ref>PMID:11447122</ref> <ref>PMID:15652481</ref>   With S5 and S12 plays an important role in translational accuracy; many suppressors of streptomycin-dependent mutants of protein S12 are found in this protein, some but not all of which decrease translational accuracy (ram, ribosomal ambiguity mutations).<ref>PMID:2461734</ref> <ref>PMID:11447122</ref> <ref>PMID:15652481</ref>   Plays a role in mRNA unwinding by the ribosome, possibly by forming part of a processivity clamp.<ref>PMID:2461734</ref> <ref>PMID:11447122</ref> <ref>PMID:15652481</ref>   Protein S4 is also a translational repressor protein, it controls the translation of the alpha-operon (which codes for S13, S11, S4, RNA polymerase alpha subunit, and L17) by binding to its mRNA.<ref>PMID:2461734</ref> <ref>PMID:11447122</ref> <ref>PMID:15652481</ref>   Also functions as a rho-dependent antiterminator of rRNA transcription, increasing the synthesis of rRNA under conditions of excess protein, allowing a more rapid return to homeostasis. Binds directly to RNA polymerase.<ref>PMID:2461734</ref> <ref>PMID:11447122</ref> <ref>PMID:15652481</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Nascent polypeptides can induce ribosome stalling, regulating downstream genes. Stalling of ErmBL peptide translation in the presence of the macrolide antibiotic erythromycin leads to resistance in Streptococcus sanguis. To reveal this stalling mechanism we obtained 3.6-A-resolution cryo-EM structures of ErmBL-stalled ribosomes with erythromycin. The nascent peptide adopts an unusual conformation with the C-terminal Asp10 side chain in a previously unseen rotated position. Together with molecular dynamics simulations, the structures indicate that peptide-bond formation is inhibited by displacement of the peptidyl-tRNA A76 ribose from its canonical position, and by non-productive interactions of the A-tRNA Lys11 side chain with the A-site crevice. These two effects combine to perturb peptide-bond formation by increasing the distance between the attacking Lys11 amine and the Asp10 carbonyl carbon. The interplay between drug, peptide and ribosome uncovered here also provides insight into the fundamental mechanism of peptide-bond formation.
-Authors: Arenz, S., Bock, L.V., Graf, M., Innis, C.A., Beckmann, R., Grubmueller, H., Vaiana, A.C., Wilson, D.N.
+A combined cryo-EM and molecular dynamics approach reveals the mechanism of ErmBL-mediated translation arrest.,Arenz S, Bock LV, Graf M, Innis CA, Beckmann R, Grubmuller H, Vaiana AC, Wilson DN Nat Commun. 2016 Jul 6;7:12026. doi: 10.1038/ncomms12026. PMID:27380950<ref>PMID:27380950</ref>
-Description: Cryo-EM structure of an ErmBL-stalled ribosome in complex with P-, and E-tRNA
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Arenz, S]]
+<div class="pdbe-citations 5ju8" style="background-color:#fffaf0;"></div>
-[[Category: Beckmann, R]]
-[[Category: Innis, C.A]]
+==See Also==
-[[Category: Graf, M]]
+*[[Ribosome 3D structures|Ribosome 3D structures]]
-[[Category: Bock, L.V]]
+== References ==
-[[Category: Grubmueller, H]]
+<references/>
-[[Category: Wilson, D.N]]
+__TOC__
-[[Category: Vaiana, A.C]]
+</SX>
+[[Category: Escherichia coli K-12]]
+[[Category: Large Structures]]
+[[Category: Arenz S]]
+[[Category: Beckmann R]]
+[[Category: Bock LV]]
+[[Category: Graf M]]
+[[Category: Grubmueller H]]
+[[Category: Innis CA]]
+[[Category: Vaiana AC]]
+[[Category: Wilson DN]]

5ju8: Difference between revisions

Latest revision as of 05:13, 24 June 2026

Cryo-EM structure of an ErmBL-stalled ribosome in complex with P-, and E-tRNA

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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