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| - | {{Large structure}}
| + | ==Crystal structure of the bacterial ribosome from Escherichia coli in complex with paromomycin and ribosome recycling factor (RRF). This file contains the 50S subunit of the first 70S ribosome, with paromomycin and RRF bound. The entire crystal structure contains two 70S ribosomes and is described in remark 400.== |
| - | {{STRUCTURE_2z4l| PDB=2z4l | SCENE= }}
| + | <StructureSection load='2z4l' size='340' side='right' caption='[[2z4l]], [[Resolution|resolution]] 4.45Å' scene=''> |
| - | ===Crystal structure of the bacterial ribosome from Escherichia coli in complex with paromomycin and ribosome recycling factor (RRF). This file contains the 50S subunit of the first 70S ribosome, with paromomycin and RRF bound. The entire crystal structure contains two 70S ribosomes and is described in remark 400.===
| + | == Structural highlights == |
| - | {{ABSTRACT_PUBMED_17660832}}
| + | <table><tr><td colspan='2'>[[2z4l]] is a 31 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [http://en.wikipedia.org/wiki/Thermus_thermophilus Thermus thermophilus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Z4L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2Z4L FirstGlance]. <br> |
| | + | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PAR:PAROMOMYCIN'>PAR</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br> |
| | + | <tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2z4k|2z4k]], [[2z4m|2z4m]], [[2z4n|2z4n]]</td></tr> |
| | + | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2z4l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2z4l OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2z4l RCSB], [http://www.ebi.ac.uk/pdbsum/2z4l PDBsum]</span></td></tr> |
| | + | <table> |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/z4/2z4l_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | Aminoglycosides are widely used antibiotics that cause messenger RNA decoding errors, block mRNA and transfer RNA translocation, and inhibit ribosome recycling. Ribosome recycling follows the termination of protein synthesis and is aided by ribosome recycling factor (RRF) in bacteria. The molecular mechanism by which aminoglycosides inhibit ribosome recycling is unknown. Here we show in X-ray crystal structures of the Escherichia coli 70S ribosome that RRF binding causes RNA helix H69 of the large ribosomal subunit, which is crucial for subunit association, to swing away from the subunit interface. Aminoglycosides bind to H69 and completely restore the contacts between ribosomal subunits that are disrupted by RRF. These results provide a structural explanation for aminoglycoside inhibition of ribosome recycling. |
| | | | |
| - | ==Function==
| + | Structural basis for aminoglycoside inhibition of bacterial ribosome recycling.,Borovinskaya MA, Pai RD, Zhang W, Schuwirth BS, Holton JM, Hirokawa G, Kaji H, Kaji A, Cate JH Nat Struct Mol Biol. 2007 Aug;14(8):727-32. Epub 2007 Jul 29. PMID:17660832<ref>PMID:17660832</ref> |
| - | [[http://www.uniprot.org/uniprot/RRF_THET8 RRF_THET8]] Responsible for the release of ribosomes from messenger RNA at the termination of protein biosynthesis. May increase the efficiency of translation by recycling ribosomes from one round of translation to another (By similarity). [[http://www.uniprot.org/uniprot/RL17_ECOLI RL17_ECOLI]] Requires L15 for assembly into the 50S subunit.[HAMAP-Rule:MF_01368] [[http://www.uniprot.org/uniprot/RL19_ECOLI RL19_ECOLI]] This protein is located at the 30S-50S ribosomal subunit interface. In the 70S ribosome (PubMed:12809609) it has been modeled to make two contacts with the 16S rRNA of the 30S subunit forming part of bridges B6 and B8. In the 3.5 A resolved structures (PubMed:16272117) L14 and L19 interact and together make contact with the 16S rRNA. The protein conformation is quite different between the 50S and 70S structures, which may be necessary for translocation.[HAMAP-Rule:MF_00402] [[http://www.uniprot.org/uniprot/RL5_ECOLI RL5_ECOLI]] 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. Its 5S rRNA binding is significantly enhanced in the presence of L18.[HAMAP-Rule:MF_01333_B] In the 70S ribosome in the initiation state (PubMed:12809609) was modeled to contact protein S13 of the 30S subunit (bridge B1b), connecting the 2 subunits; the protein-protein contacts between S13 and L5 in B1b change in the model with bound EF-G implicating this bridge in subunit movement (PubMed:12809609 and PubMed:18723842). In the two 3.5 A resolved ribosome structures (PubMed:16272117) the contacts between L5, S13 and S19 are different, confirming the dynamic nature of this interaction.[HAMAP-Rule:MF_01333_B] 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/RL16_ECOLI RL16_ECOLI]] This protein binds directly to 23S ribosomal RNA and is located at the A site of the peptidyltransferase center. It contacts the A and P site tRNAs. It has an essential role in subunit assembly, which is not well understood.[HAMAP-Rule:MF_01342] [[http://www.uniprot.org/uniprot/RL29_ECOLI RL29_ECOLI]] Binds 23S rRNA. It is not essential for growth.[HAMAP-Rule:MF_00374] One of the proteins that surrounds the polypeptide exit tunnel on the outside of the subunit. Contacts trigger factor (PubMed:12226666).[HAMAP-Rule:MF_00374] [[http://www.uniprot.org/uniprot/RL15_ECOLI RL15_ECOLI]] This protein binds the 5S rRNA. It is required for the late stages of subunit assembly, and is essential for 5S rRNA assembly onto the ribosome.[HAMAP-Rule:MF_01341_B] [[http://www.uniprot.org/uniprot/RL6_ECOLI RL6_ECOLI]] This protein binds directly to at least 2 domains of the 23S ribosomal RNA, thus 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] Gentamicin-resistant mutations in this protein affect translation fidelity.[HAMAP-Rule:MF_01365] [[http://www.uniprot.org/uniprot/RL24_ECOLI RL24_ECOLI]] 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. It is not thought to be involved in the functions of the mature 50S subunit in vitro.<ref>PMID:357435</ref> One of the proteins that surrounds the polypeptide exit tunnel on the outside of the subunit.<ref>PMID:357435</ref> [[http://www.uniprot.org/uniprot/RL21_ECOLI RL21_ECOLI]] This protein binds to 23S rRNA in the presence of protein L20.[HAMAP-Rule:MF_01363] [[http://www.uniprot.org/uniprot/RL13_ECOLI RL13_ECOLI]] 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] [[http://www.uniprot.org/uniprot/RL25_ECOLI RL25_ECOLI]] This is one of the proteins that binds to the 5S RNA in the ribosome where it forms part of the central protuberance. Binds to the 5S rRNA independently of L5 and L18. Not required for binding of the 5S rRNA/L5/L18 subcomplex to 23S rRNA.[HAMAP-Rule:MF_01336] [[http://www.uniprot.org/uniprot/RL22_ECOLI RL22_ECOLI]] 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_B] The globular domain of the protein is one of the proteins that surrounds the polypeptide exit tunnel on the outside of the subunit, while an extended beta-hairpin is found that penetrates into the center of the 70S ribosome where it lines the wall of the exit tunnel. Removal of most of this hairpin (residues 85-95) does not prevent its incorporation into 70S ribosomes. Two of the hairpin residues (91 and 93) seem to be involved in translation elongation arrest of the SecM protein, as their replacement by larger amino acids alleviates the arrest.[HAMAP-Rule:MF_01331_B] [[http://www.uniprot.org/uniprot/RL18_ECOLI RL18_ECOLI]] This is one of the proteins that mediates the attachment of the 5S rRNA subcomplex onto the large ribosomal subunit where it forms part of the central protuberance. Binds stably to 5S rRNA; increases binding abilities of L5 in a cooperative fashion; both proteins together confer 23S rRNA binding. The 5S rRNA and some of its associated proteins might help stabilize positioning of ribosome-bound tRNAs.<ref>PMID:353728</ref> [[http://www.uniprot.org/uniprot/RL20_ECOLI RL20_ECOLI]] One of the primary rRNA binding proteins, it binds close to the 5'-end of the 23S rRNA. It is important during the early stages of 50S assembly.[HAMAP-Rule:MF_00382] [[http://www.uniprot.org/uniprot/RL23_ECOLI RL23_ECOLI]] One of the early assembly proteins, it binds 23S rRNA; is essential for growth. One of the proteins that surround the polypeptide exit tunnel on the outside of the subunit. Acts as the docking site for trigger factor (PubMed:12226666) for Ffh binding to the ribosome (SRP54, PubMed:12756233 and PubMed:12702815) and to nascent polypeptide chains (PubMed:12756233).[HAMAP-Rule:MF_01369] [[http://www.uniprot.org/uniprot/RL14_ECOLI RL14_ECOLI]] This protein binds directly to 23S ribosomal RNA. In the E.coli 70S ribosome (PubMed:12809609) it has been modeled to make two contacts with the 16S rRNA of the 30S subunit, forming part of bridges B5 and B8, connecting the 2 subunits. Although the protein undergoes significant rotation during the transition from an initiation to and EF-G bound state, the bridges remain stable. In the 3.5 A resolved structures (PubMed:16272117) L14 and L19 interact and together make contact with the 16S rRNA in bridges B5 and B8.<ref>PMID:22829778</ref> Can also interact with RsfA, in this case bridge B8 probably cannot form, and the 30S and 50S ribosomal subunits do not associate, which represses translation.<ref>PMID:22829778</ref> [[http://www.uniprot.org/uniprot/RL11_ECOLI RL11_ECOLI]] This protein binds directly to 23S ribosomal RNA. Forms the L11 stalk, which is mobile in the ribosome, indicating its contribution to the activity of initiation, elongation and release factors.[HAMAP-Rule:MF_00736_B] [[http://www.uniprot.org/uniprot/RL4_ECOLI RL4_ECOLI]] 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.<ref>PMID:2442760</ref> Protein L4 is a both a transcriptional repressor and a translational repressor protein; these two functions are independent of each other. It regulates transcription of the S10 operon (to which L4 belongs) by causing premature termination of transcription within the S10 leader; termination absolutely requires the NusA protein. L4 controls the translation of the S10 operon by binding to its mRNA. The regions of L4 that control regulation (residues 131-210) are different from those required for ribosome assembly (residues 89-103).<ref>PMID:2442760</ref> Forms part of the polypeptide exit tunnel.<ref>PMID:2442760</ref> Can regulate expression from Citrobacter freundii, Haemophilus influenzae, Morganella morganii, Salmonella typhimurium, Serratia marcescens, Vibrio cholerae and Yersinia enterocolitica (but not Pseudomonas aeruginosa) S10 leaders in vitro.<ref>PMID:2442760</ref> [[http://www.uniprot.org/uniprot/RL2_ECOLI RL2_ECOLI]] One of the primary rRNA binding proteins. Located near the base of the L1 stalk, it is probably also mobile. 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 highly controversial.[HAMAP-Rule:MF_01320_B] In the E.coli 70S ribosome in the initiation state it has been modeled to make several contacts with the 16S rRNA (forming bridge B7b, PubMed:12809609); these contacts are broken in the model with bound EF-G.[HAMAP-Rule:MF_01320_B] [[http://www.uniprot.org/uniprot/RL9_ECOLI RL9_ECOLI]] One of the primary rRNA binding proteins, it binds very close to the 3' end of the 23S rRNA.[HAMAP-Rule:MF_00503] [[http://www.uniprot.org/uniprot/RL3_ECOLI RL3_ECOLI]] One of two assembly inititator proteins, it binds directly near the 3'-end of the 23S rRNA, where it nucleates assembly of the 50S subunit.[HAMAP-Rule:MF_01325_B]
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| | | | |
| - | ==About this Structure==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | [[2z4l]] is a 31 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [http://en.wikipedia.org/wiki/Thermus_thermophilus Thermus thermophilus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Z4L OCA].
| + | </div> |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Ribosomal protein L11|Ribosomal protein L11]]
| + | *[[Ribosome 3D structures|Ribosome 3D structures]] |
| - | *[[Ribosomal protein L13|Ribosomal protein L13]]
| + | == References == |
| - | *[[Ribosomal protein L14|Ribosomal protein L14]]
| + | <references/> |
| - | *[[Ribosomal protein L15|Ribosomal protein L15]]
| + | __TOC__ |
| - | *[[Ribosomal protein L16|Ribosomal protein L16]]
| + | </StructureSection> |
| - | *[[Ribosomal protein L17|Ribosomal protein L17]]
| + | |
| - | *[[Ribosomal protein L18|Ribosomal protein L18]]
| + | |
| - | *[[Ribosomal protein L19|Ribosomal protein L19]]
| + | |
| - | *[[Ribosomal protein L2|Ribosomal protein L2]]
| + | |
| - | *[[Ribosomal protein L20|Ribosomal protein L20]]
| + | |
| - | *[[Ribosomal protein L21|Ribosomal protein L21]]
| + | |
| - | *[[Ribosomal protein L22|Ribosomal protein L22]]
| + | |
| - | *[[Ribosomal protein L23|Ribosomal protein L23]]
| + | |
| - | *[[Ribosomal protein L24|Ribosomal protein L24]]
| + | |
| - | *[[Ribosomal protein L25|Ribosomal protein L25]]
| + | |
| - | *[[Ribosomal protein L27|Ribosomal protein L27]]
| + | |
| - | *[[Ribosomal protein L28|Ribosomal protein L28]]
| + | |
| - | *[[Ribosomal protein L29|Ribosomal protein L29]]
| + | |
| - | *[[Ribosomal protein L3|Ribosomal protein L3]]
| + | |
| - | *[[Ribosomal protein L30|Ribosomal protein L30]]
| + | |
| - | *[[Ribosomal protein L32|Ribosomal protein L32]]
| + | |
| - | *[[Ribosomal protein L33|Ribosomal protein L33]]
| + | |
| - | *[[Ribosomal protein L34|Ribosomal protein L34]]
| + | |
| - | *[[Ribosomal protein L35|Ribosomal protein L35]]
| + | |
| - | *[[Ribosomal protein L36|Ribosomal protein L36]]
| + | |
| - | *[[Ribosomal protein L4|Ribosomal protein L4]]
| + | |
| - | *[[Ribosomal protein L5|Ribosomal protein L5]]
| + | |
| - | *[[Ribosomal protein L6|Ribosomal protein L6]]
| + | |
| - | *[[Ribosomal protein L9|Ribosomal protein L9]]
| + | |
| - | *[[Ribosome|Ribosome]] | + | |
| - | | + | |
| - | ==Reference== | + | |
| - | <ref group="xtra">PMID:017660832</ref><references group="xtra"/><references/>
| + | |
| | [[Category: Escherichia coli]] | | [[Category: Escherichia coli]] |
| | [[Category: Thermus thermophilus]] | | [[Category: Thermus thermophilus]] |
