5t7v | pdb_00005t7v
Methicillin Resistant, Linezolid resistant Staphylococcus aureus 70S ribosome (delta S145 uL3)
Structural highlights
Function[W8TUB4_STAAU] 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] [A0A077VLD5_STAAU] One of the primary rRNA binding proteins, it binds specifically to the 5'-end of 16S ribosomal RNA.[HAMAP-Rule:MF_01345] [B3VKN3_STAAU] 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] [A0A0H2K0A0_STAAU] Involved in the binding of tRNA to the ribosomes.[HAMAP-Rule:MF_00508] [A0A077VMP6_STAAU] 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] [A0A077UVB6_STAAU] 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.[HAMAP-Rule:MF_00402][RuleBase:RU000559] [W8U3W0_STAAU] 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] [A0A077UKF9_STAAU] 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] [W8TVK2_STAAU] 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] [A0A0U1MRH3_STAAU] 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] [W8TUC9_STAAU] 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:SAAS00382364] With S4 and S12 plays an important role in translational accuracy.[HAMAP-Rule:MF_01307][SAAS:SAAS00382324] [W8TRD5_STAAU] 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] [W8U8T8_STAAU] 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] [A0A077V4G0_STAAU] Binds 23S rRNA and is also seen to make contacts with the A and possibly P site tRNAs.[HAMAP-Rule:MF_01342][RuleBase:RU004414] [W8TUE6_STAAU] 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] [A0A077UKD6_STAAU] 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] [A0A1K8EL93_STAAU] Binds directly to 16S ribosomal RNA.[HAMAP-Rule:MF_00500] [W8TRE0_STAAU] 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] [W8TPC6_STAAU] Binds together with S18 to 16S ribosomal RNA.[HAMAP-Rule:MF_00360][SAAS:SAAS00348112] [A0A077UGA7_STAAU] Binds to the 23S rRNA.[HAMAP-Rule:MF_01341][SAAS:SAAS00687840] [A0A1D4K9U8_STAAU] 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] [W8U1C6_STAAU] 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] [W8TRC7_STAAU] 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] [A0A077UUA0_STAAU] Binds to 23S rRNA. Forms part of two intersubunit bridges in the 70S ribosome.[HAMAP-Rule:MF_01367][RuleBase:RU003950] [D7URR3_STAAU] This protein binds to 23S rRNA in the presence of protein L20.[HAMAP-Rule:MF_01363][RuleBase:RU000562] [W8U6H8_STAAU] 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] Publication Abstract from PubMedAn 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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