4wfn

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{{Large structure}}
==Crystal structure of the large ribosomal subunit (50S) of Deinococcus radiodurans containing a three residue insertion in L22 in complex with erythromycin==
==Crystal structure of the large ribosomal subunit (50S) of Deinococcus radiodurans containing a three residue insertion in L22 in complex with erythromycin==
<StructureSection load='4wfn' size='340' side='right' caption='[[4wfn]], [[Resolution|resolution]] 3.54&Aring;' scene=''>
<StructureSection load='4wfn' size='340' side='right' caption='[[4wfn]], [[Resolution|resolution]] 3.54&Aring;' scene=''>
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<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='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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4u67|4u67]]</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4u67|4u67]]</td></tr>
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<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=4wfn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wfn OCA], [http://pdbe.org/4wfn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4wfn RCSB], [http://www.ebi.ac.uk/pdbsum/4wfn PDBsum]</span></td></tr>
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<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=4wfn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wfn OCA], [http://pdbe.org/4wfn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4wfn RCSB], [http://www.ebi.ac.uk/pdbsum/4wfn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4wfn ProSAT]</span></td></tr>
</table>
</table>
{{Large structure}}
{{Large structure}}
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/RL18_DEIRA RL18_DEIRA]] This is one of the proteins that binds and mediates the attachment of the 5S RNA into the large ribosomal subunit, where it forms part of the central protuberance.[HAMAP-Rule:MF_01337_B] [[http://www.uniprot.org/uniprot/RL29_DEIRA RL29_DEIRA]] Binds the 23S rRNA. One of the proteins that surrounds the polypeptide exit tunnel on the outside of the subunit.[HAMAP-Rule:MF_00374] [[http://www.uniprot.org/uniprot/RL14_DEIRA RL14_DEIRA]] Forms part of two intersubunit bridges in the 70S ribosome (By similarity). Binds to 23S rRNA.[HAMAP-Rule:MF_01367] [[http://www.uniprot.org/uniprot/RL35_DEIRA RL35_DEIRA]] Binds the 23S rRNA.[HAMAP-Rule:MF_00514] [[http://www.uniprot.org/uniprot/RL3_DEIRA RL3_DEIRA]] 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 (By similarity).[HAMAP-Rule:MF_01325_B] [[http://www.uniprot.org/uniprot/RL24_DEIRA RL24_DEIRA]] 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 (By similarity).[HAMAP-Rule:MF_01326_B] One of the proteins that surrounds the polypeptide exit tunnel on the outside of the subunit. Contacts trigger factor (TF) when it is bound to the ribosome; this contact may expose a hydrophobic crevice in TF (PubMed:16271892).[HAMAP-Rule:MF_01326_B] [[http://www.uniprot.org/uniprot/RL30_DEIRA RL30_DEIRA]] Binds the 5S and 23S rRNAs.[HAMAP-Rule:MF_01371] [[http://www.uniprot.org/uniprot/RL2_DEIRA RL2_DEIRA]] 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 (By similarity).[HAMAP-Rule:MF_01320_B] [[http://www.uniprot.org/uniprot/RL25_DEIRA RL25_DEIRA]] This is one of 3 proteins that mediate the attachment of the 5S rRNA onto the large ribosomal subunit. This protein has three domains. The N-terminal one is bound on the solvent face, the middle domain fills the space between the 5S rRNA and the L11 arm contacting the 23S rRNA while the C-terminal domain is on the edge of the intersubunit interface and contacts the A site. The protein conformation changes upon binding of a tRNA mimic to the A site, although the mimic does not interact directly with CTC itself, consistent with CTCs presumed role in moderating A site binding.[HAMAP-Rule:MF_01334] [[http://www.uniprot.org/uniprot/RL32_DEIRA RL32_DEIRA]] Forms a cluster with L17 and L22, and with L22, a pair of "tweezers" that hold together all the domains of the 23S rRNA. Interacts with the antibiotic troleandomycin which blocks the peptide exit tunnel.[HAMAP-Rule:MF_00340] [[http://www.uniprot.org/uniprot/RL20_DEIRA RL20_DEIRA]] Binds directly to 23S rRNA, probably serving to organize its structure.[HAMAP-Rule:MF_00382] [[http://www.uniprot.org/uniprot/RL23_DEIRA RL23_DEIRA]] One of the early assembly protein (By similarity) it binds 23S rRNA. One of the proteins that surrounds the polypeptide exit tunnel on the outside of the subunit. Forms the main docking site for trigger factor binding to the ribosome (PubMed:16091460 and PubMed:16271892).[HAMAP-Rule:MF_01369] [[http://www.uniprot.org/uniprot/RL13_DEIRA RL13_DEIRA]] This protein is one of the early assembly proteins of the 50S ribosomal subunit (By similarity). Binds to the 23S rRNA.[HAMAP-Rule:MF_01366_B] [[http://www.uniprot.org/uniprot/RL34_DEIRA RL34_DEIRA]] Binds the 23S rRNA.[HAMAP-Rule:MF_00391] [[http://www.uniprot.org/uniprot/RL4_DEIRA RL4_DEIRA]] 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 (By similarity).[HAMAP-Rule:MF_01328_B] Makes multiple contacts with different domains of the 23S rRNA in the assembled 50S subunit.[HAMAP-Rule:MF_01328_B] This protein is located close to the polypeptide exit tunnel, and interacts with the modified macrolide azithromycin, which blocks the tunnel.[HAMAP-Rule:MF_01328_B] [[http://www.uniprot.org/uniprot/RL16_DEIRA RL16_DEIRA]] Binds the 5S and 23S rRNAs and is also seen to make contacts with the A and P site tRNAs. Interacts with A site tRNA mimics, and is probably one of the key factors, along with a helix of the 23S rRNA, in positioning tRNA stems in the peptidyl-transferase center.[HAMAP-Rule:MF_01342] [[http://www.uniprot.org/uniprot/RL19_DEIRA RL19_DEIRA]] This protein is located at the 30S-50S ribosomal subunit interface and may play a role in the structure and function of the aminoacyl-tRNA binding site (By similarity). Binds the 23S rRNA.[HAMAP-Rule:MF_00402] [[http://www.uniprot.org/uniprot/RL21_DEIRA RL21_DEIRA]] Binds directly to 23S rRNA, probably serving to organize its structure.[HAMAP-Rule:MF_01363] [[http://www.uniprot.org/uniprot/RL22_DEIRA RL22_DEIRA]] 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 (By similarity).[HAMAP-Rule:MF_01331_B] The globular domain of the protein is located by the polypeptide exit tunnel on the outside of the subunit while an extended beta-hairpin forms part of the wall of the tunnel. Forms a pair of "tweezers" with L32 that hold together two different domains of the 23S rRNA. Interacts with the tunnel-blocking modified macrolide azithromycin. Upon binding of the macrolide troleadomycin to the ribosome, the tip of the beta-hairpin is displaced, which severely restricts the tunnel. This and experiments in E.coli have led to the suggestion that it is part of the gating mechanism involved in translation arrest in the absence of the protein export system.[HAMAP-Rule:MF_01331_B] [[http://www.uniprot.org/uniprot/RL15_DEIRA RL15_DEIRA]] Binds to the 23S rRNA.[HAMAP-Rule:MF_01341_B] [[http://www.uniprot.org/uniprot/RL5_DEIRA RL5_DEIRA]] 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 (By similarity). 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_B] [[http://www.uniprot.org/uniprot/RL33_DEIRA RL33_DEIRA]] Binds the 23S rRNA and the E site tRNA.[HAMAP-Rule:MF_00294] [[http://www.uniprot.org/uniprot/RL17_DEIRA RL17_DEIRA]] Binds to the 23S rRNA.[HAMAP-Rule:MF_01368] [[http://www.uniprot.org/uniprot/RL27_DEIRA RL27_DEIRA]] Binds the 5S and 23S rRNAs and also the tRNA in the P site.[HAMAP-Rule:MF_00539] [[http://www.uniprot.org/uniprot/RL6_DEIRA RL6_DEIRA]] 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 (By similarity). This protein binds to the 23S rRNA, and is important in its secondary structure.[HAMAP-Rule:MF_01365]
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[[http://www.uniprot.org/uniprot/RL18_DEIRA RL18_DEIRA]] This is one of the proteins that binds and mediates the attachment of the 5S RNA into the large ribosomal subunit, where it forms part of the central protuberance.[HAMAP-Rule:MF_01337_B] [[http://www.uniprot.org/uniprot/RL29_DEIRA RL29_DEIRA]] Binds the 23S rRNA. One of the proteins that surrounds the polypeptide exit tunnel on the outside of the subunit.[HAMAP-Rule:MF_00374] [[http://www.uniprot.org/uniprot/RL14_DEIRA RL14_DEIRA]] Forms part of two intersubunit bridges in the 70S ribosome (By similarity). Binds to 23S rRNA.[HAMAP-Rule:MF_01367] [[http://www.uniprot.org/uniprot/RL35_DEIRA RL35_DEIRA]] Binds the 23S rRNA.[HAMAP-Rule:MF_00514] [[http://www.uniprot.org/uniprot/RL24_DEIRA RL24_DEIRA]] 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 (By similarity).[HAMAP-Rule:MF_01326_B] One of the proteins that surrounds the polypeptide exit tunnel on the outside of the subunit. Contacts trigger factor (TF) when it is bound to the ribosome; this contact may expose a hydrophobic crevice in TF (PubMed:16271892).[HAMAP-Rule:MF_01326_B] [[http://www.uniprot.org/uniprot/RL3_DEIRA RL3_DEIRA]] 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 (By similarity).[HAMAP-Rule:MF_01325_B] [[http://www.uniprot.org/uniprot/RL30_DEIRA RL30_DEIRA]] Binds the 5S and 23S rRNAs.[HAMAP-Rule:MF_01371] [[http://www.uniprot.org/uniprot/RL2_DEIRA RL2_DEIRA]] 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 (By similarity).[HAMAP-Rule:MF_01320_B] [[http://www.uniprot.org/uniprot/RL25_DEIRA RL25_DEIRA]] This is one of 3 proteins that mediate the attachment of the 5S rRNA onto the large ribosomal subunit. This protein has three domains. The N-terminal one is bound on the solvent face, the middle domain fills the space between the 5S rRNA and the L11 arm contacting the 23S rRNA while the C-terminal domain is on the edge of the intersubunit interface and contacts the A site. The protein conformation changes upon binding of a tRNA mimic to the A site, although the mimic does not interact directly with CTC itself, consistent with CTCs presumed role in moderating A site binding.[HAMAP-Rule:MF_01334] [[http://www.uniprot.org/uniprot/RL32_DEIRA RL32_DEIRA]] Forms a cluster with L17 and L22, and with L22, a pair of "tweezers" that hold together all the domains of the 23S rRNA. Interacts with the antibiotic troleandomycin which blocks the peptide exit tunnel.[HAMAP-Rule:MF_00340] [[http://www.uniprot.org/uniprot/RL23_DEIRA RL23_DEIRA]] One of the early assembly protein (By similarity) it binds 23S rRNA. One of the proteins that surrounds the polypeptide exit tunnel on the outside of the subunit. Forms the main docking site for trigger factor binding to the ribosome (PubMed:16091460 and PubMed:16271892).[HAMAP-Rule:MF_01369] [[http://www.uniprot.org/uniprot/RL20_DEIRA RL20_DEIRA]] Binds directly to 23S rRNA, probably serving to organize its structure.[HAMAP-Rule:MF_00382] [[http://www.uniprot.org/uniprot/RL34_DEIRA RL34_DEIRA]] Binds the 23S rRNA.[HAMAP-Rule:MF_00391] [[http://www.uniprot.org/uniprot/RL13_DEIRA RL13_DEIRA]] This protein is one of the early assembly proteins of the 50S ribosomal subunit (By similarity). Binds to the 23S rRNA.[HAMAP-Rule:MF_01366_B] [[http://www.uniprot.org/uniprot/RL4_DEIRA RL4_DEIRA]] 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 (By similarity).[HAMAP-Rule:MF_01328_B] Makes multiple contacts with different domains of the 23S rRNA in the assembled 50S subunit.[HAMAP-Rule:MF_01328_B] This protein is located close to the polypeptide exit tunnel, and interacts with the modified macrolide azithromycin, which blocks the tunnel.[HAMAP-Rule:MF_01328_B] [[http://www.uniprot.org/uniprot/RL16_DEIRA RL16_DEIRA]] Binds the 5S and 23S rRNAs and is also seen to make contacts with the A and P site tRNAs. Interacts with A site tRNA mimics, and is probably one of the key factors, along with a helix of the 23S rRNA, in positioning tRNA stems in the peptidyl-transferase center.[HAMAP-Rule:MF_01342] [[http://www.uniprot.org/uniprot/RL19_DEIRA RL19_DEIRA]] This protein is located at the 30S-50S ribosomal subunit interface and may play a role in the structure and function of the aminoacyl-tRNA binding site (By similarity). Binds the 23S rRNA.[HAMAP-Rule:MF_00402] [[http://www.uniprot.org/uniprot/RL21_DEIRA RL21_DEIRA]] Binds directly to 23S rRNA, probably serving to organize its structure.[HAMAP-Rule:MF_01363] [[http://www.uniprot.org/uniprot/RL22_DEIRA RL22_DEIRA]] 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 (By similarity).[HAMAP-Rule:MF_01331_B] The globular domain of the protein is located by the polypeptide exit tunnel on the outside of the subunit while an extended beta-hairpin forms part of the wall of the tunnel. Forms a pair of "tweezers" with L32 that hold together two different domains of the 23S rRNA. Interacts with the tunnel-blocking modified macrolide azithromycin. Upon binding of the macrolide troleadomycin to the ribosome, the tip of the beta-hairpin is displaced, which severely restricts the tunnel. This and experiments in E.coli have led to the suggestion that it is part of the gating mechanism involved in translation arrest in the absence of the protein export system.[HAMAP-Rule:MF_01331_B] [[http://www.uniprot.org/uniprot/RL15_DEIRA RL15_DEIRA]] Binds to the 23S rRNA.[HAMAP-Rule:MF_01341_B] [[http://www.uniprot.org/uniprot/RL5_DEIRA RL5_DEIRA]] 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 (By similarity). 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_B] [[http://www.uniprot.org/uniprot/RL33_DEIRA RL33_DEIRA]] Binds the 23S rRNA and the E site tRNA.[HAMAP-Rule:MF_00294] [[http://www.uniprot.org/uniprot/RL27_DEIRA RL27_DEIRA]] Binds the 5S and 23S rRNAs and also the tRNA in the P site.[HAMAP-Rule:MF_00539] [[http://www.uniprot.org/uniprot/RL17_DEIRA RL17_DEIRA]] Binds to the 23S rRNA.[HAMAP-Rule:MF_01368] [[http://www.uniprot.org/uniprot/RL6_DEIRA RL6_DEIRA]] 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 (By similarity). This protein binds to the 23S rRNA, and is important in its secondary structure.[HAMAP-Rule:MF_01365]
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Erythromycin is a clinically useful antibiotic that binds to an rRNA pocket in the ribosomal exit tunnel. Commonly, resistance to erythromycin is acquired by alterations of rRNA nucleotides that interact with the drug. Mutations in the beta hairpin of ribosomal protein uL22, which is rather distal to the erythromycin binding site, also generate resistance to the antibiotic. We have determined the crystal structure of the large ribosomal subunit from Deinococcus radiodurans with a three amino acid insertion within the beta hairpin of uL22 that renders resistance to erythromycin. The structure reveals a shift of the beta hairpin of the mutated uL22 toward the interior of the exit tunnel, triggering a cascade of structural alterations of rRNA nucleotides that propagate to the erythromycin binding pocket. Our findings support recent studies showing that the interactions between uL22 and specific sequences within nascent chains trigger conformational rearrangements in the exit tunnel.
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The Ribosomal Protein uL22 Modulates the Shape of the Protein Exit Tunnel.,Wekselman I, Zimmerman E, Davidovich C, Belousoff M, Matzov D, Krupkin M, Rozenberg H, Bashan A, Friedlander G, Kjeldgaard J, Ingmer H, Lindahl L, Zengel JM, Yonath A Structure. 2017 Aug 1;25(8):1233-1241.e3. doi: 10.1016/j.str.2017.06.004. Epub, 2017 Jul 6. PMID:28689968<ref>PMID:28689968</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 4wfn" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>

Revision as of 06:07, 17 August 2017

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Crystal structure of the large ribosomal subunit (50S) of Deinococcus radiodurans containing a three residue insertion in L22 in complex with erythromycin

4wfn, resolution 3.54Å

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