View source for 5tcu


==Methicillin sensitive Staphylococcus aureus 70S ribosome==
<SX load='5tcu' size='340' side='right' viewer='molstar' caption='[[5tcu]], [[Resolution|resolution]] 3.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5tcu]] is a 52 chain structure with sequence from [http://en.wikipedia.org/wiki/Staa8 Staa8] and [http://en.wikipedia.org/wiki/Staphylococcus_aureus_(strain_nctc_8325) Staphylococcus aureus (strain nctc 8325)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TCU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TCU 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=PAR:PAROMOMYCIN'>PAR</scene></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=5tcu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tcu OCA], [http://pdbe.org/5tcu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tcu RCSB], [http://www.ebi.ac.uk/pdbsum/5tcu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tcu ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/RL16_STAA8 RL16_STAA8]] Binds 23S rRNA and is also seen to make contacts with the A and possibly P site tRNAs. [[http://www.uniprot.org/uniprot/RL15_STAA8 RL15_STAA8]] Binds to the 23S rRNA. [[http://www.uniprot.org/uniprot/RS8_STAA8 RS8_STAA8]] 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. [[http://www.uniprot.org/uniprot/RL3_STAA8 RL3_STAA8]] 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. [[http://www.uniprot.org/uniprot/RS3_STAA8 RS3_STAA8]] Binds the lower part of the 30S subunit head. Binds mRNA in the 70S ribosome, positioning it for translation. [[http://www.uniprot.org/uniprot/RS18_STAA8 RS18_STAA8]] 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. [[http://www.uniprot.org/uniprot/RS19_STAA8 RS19_STAA8]] Protein S19 forms a complex with S13 that binds strongly to the 16S ribosomal RNA. [[http://www.uniprot.org/uniprot/RL13_STAA8 RL13_STAA8]] 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. [[http://www.uniprot.org/uniprot/RS17_STAA8 RS17_STAA8]] One of the primary rRNA binding proteins, it binds specifically to the 5'-end of 16S ribosomal RNA. [[http://www.uniprot.org/uniprot/RL4_STAA8 RL4_STAA8]] 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.  Forms part of the polypeptide exit tunnel. [[http://www.uniprot.org/uniprot/RL2_STAA8 RL2_STAA8]] 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. [[http://www.uniprot.org/uniprot/RL5_STAA8 RL5_STAA8]] 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. [[http://www.uniprot.org/uniprot/RL23_STAA8 RL23_STAA8]] 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. [[http://www.uniprot.org/uniprot/RS15_STAA8 RS15_STAA8]] 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.  Forms an intersubunit bridge (bridge B4) with the 23S rRNA of the 50S subunit in the ribosome. [[http://www.uniprot.org/uniprot/RS11_STAA8 RS11_STAA8]] 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. [[http://www.uniprot.org/uniprot/RL14_STAA8 RL14_STAA8]] Binds to 23S rRNA. Forms part of two intersubunit bridges in the 70S ribosome. [[http://www.uniprot.org/uniprot/RL18_STAA8 RL18_STAA8]] 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. [[http://www.uniprot.org/uniprot/RS12_STAA8 RS12_STAA8]] With S4 and S5 plays an important role in translational accuracy.[HAMAP-Rule:MF_00403]  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] [[http://www.uniprot.org/uniprot/Q2G0S0_STAA8 Q2G0S0_STAA8]] 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_01334][SAAS:SAAS00023350] [[http://www.uniprot.org/uniprot/RS14Z_STAA8 RS14Z_STAA8]] 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_01364] [[http://www.uniprot.org/uniprot/RL6_STAA8 RL6_STAA8]] 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. [[http://www.uniprot.org/uniprot/RS7_STAA8 RS7_STAA8]] 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. [[http://www.uniprot.org/uniprot/RL22_STAA8 RL22_STAA8]] 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).  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. [[http://www.uniprot.org/uniprot/RS4_STAA8 RS4_STAA8]] One of the primary rRNA binding proteins, it binds directly to 16S rRNA where it nucleates assembly of the body of the 30S subunit.  With S5 and S12 plays an important role in translational accuracy. [[http://www.uniprot.org/uniprot/RL19_STAA8 RL19_STAA8]] 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. [[http://www.uniprot.org/uniprot/RS10_STAAB RS10_STAAB]] Involved in the binding of tRNA to the ribosomes. [[http://www.uniprot.org/uniprot/RL24_STAA8 RL24_STAA8]] 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.  One of the proteins that surrounds the polypeptide exit tunnel on the outside of the subunit. [[http://www.uniprot.org/uniprot/RS13_STAA8 RS13_STAA8]] 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. [[http://www.uniprot.org/uniprot/RL21_STAA8 RL21_STAA8]] This protein binds to 23S rRNA in the presence of protein L20. [[http://www.uniprot.org/uniprot/RS5_STAA8 RS5_STAA8]] With S4 and S12 plays an important role in translational accuracy.  Located at the back of the 30S subunit body where it stabilizes the conformation of the head with respect to the body. [[http://www.uniprot.org/uniprot/RL20_STAA8 RL20_STAA8]] 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. [[http://www.uniprot.org/uniprot/RS20_STAA8 RS20_STAA8]] Binds directly to 16S ribosomal RNA. [[http://www.uniprot.org/uniprot/RS6_STAA8 RS6_STAA8]] Binds together with S18 to 16S ribosomal RNA. 
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== Publication Abstract from PubMed ==
An unorthodox, surprising mechanism of resistance to the antibiotic linezolid was revealed by cryo-electron microscopy (cryo-EM) in the 70S ribosomes from a clinical isolate of Staphylococcus aureus This high-resolution structural information demonstrated that a single amino acid deletion in ribosomal protein uL3 confers linezolid resistance despite being located 24 A away from the linezolid binding pocket in the peptidyl-transferase center. The mutation induces a cascade of allosteric structural rearrangements of the rRNA that ultimately results in the alteration of the antibiotic binding site.IMPORTANCE The growing burden on human health caused by various antibiotic resistance mutations now includes prevalent Staphylococcus aureus resistance to last-line antimicrobial drugs such as linezolid and daptomycin. Structure-informed drug modification represents a frontier with respect to designing advanced clinical therapies, but success in this strategy requires rapid, facile means to shed light on the structural basis for drug resistance (D. Brown, Nat Rev Drug Discov 14:821-832, 2015, https://doi.org/10.1038/nrd4675). Here, detailed structural information demonstrates that a common mechanism is at play in linezolid resistance and provides a step toward the redesign of oxazolidinone antibiotics, a strategy that could thwart known mechanisms of linezolid resistance.

Structural Basis for Linezolid Binding Site Rearrangement in the Staphylococcus aureus Ribosome.,Belousoff MJ, Eyal Z, Radjainia M, Ahmed T, Bamert RS, Matzov D, Bashan A, Zimmerman E, Mishra S, Cameron D, Elmlund H, Peleg AY, Bhushan S, Lithgow T, Yonath A MBio. 2017 May 9;8(3). pii: e00395-17. doi: 10.1128/mBio.00395-17. PMID:28487427<ref>PMID:28487427</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5tcu" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ribosome 3D structures|Ribosome 3D structures]]
== References ==
<references/>
__TOC__
</SX>
[[Category: Large Structures]]
[[Category: Staa8]]
[[Category: Ahmed, T]]
[[Category: Bashan, A]]
[[Category: Belousoff, N]]
[[Category: Bhushan, S]]
[[Category: Eyal, Z]]
[[Category: Lithgow, T]]
[[Category: Matzov, D]]
[[Category: Mishra, S]]
[[Category: Yonath, A]]
[[Category: Zimmerman, E]]
[[Category: 70s ribosome]]
[[Category: Cryoem]]
[[Category: Ribosome]]
[[Category: Ribosome-antibiotic complex]]
[[Category: Staphylococcus aureus]]