6s0x
Erythromycin Resistant Staphylococcus aureus 70S ribosome (delta R88 A89 uL22) in complex with erythromycin.
Structural highlights
Function[A0A077UU26_STAAU] Binds the lower part of the 30S subunit head. Binds mRNA in the 70S ribosome, positioning it for translation.[HAMAP-Rule:MF_01309] [W8U3X2_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] [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] [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] [D7URR3_STAAU] This protein binds to 23S rRNA in the presence of protein L20.[HAMAP-Rule:MF_01363][RuleBase:RU000562] [A0A077UGW7_STAAU] 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][SAAS:SAAS00344925] [A0A0H2K0A0_STAAU] Involved in the binding of tRNA to the ribosomes.[HAMAP-Rule:MF_00508] [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] [A0A133Q8Z9_STAAU] 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:SAAS00720025] [A0A133PYC3_STAAU] Protein S19 forms a complex with S13 that binds strongly to the 16S ribosomal RNA.[HAMAP-Rule:MF_00531] [A0A077UGA7_STAAU] Binds to the 23S rRNA.[HAMAP-Rule:MF_01341][SAAS:SAAS00687840] [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] [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] [A0A077UZF4_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] [A0A133PZQ5_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] [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] [W8TUC3_STAAU] 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.[HAMAP-Rule:MF_01333] [W8UXC3_STAAU] Binds directly to 16S ribosomal RNA.[HAMAP-Rule:MF_00500] [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] [W8TPC6_STAAU] Binds together with S18 to 16S ribosomal RNA.[HAMAP-Rule:MF_00360][SAAS:SAAS00348112] [A0A077UUA0_STAAU] Binds to 23S rRNA. Forms part of two intersubunit bridges in the 70S ribosome.[HAMAP-Rule:MF_01367][RuleBase:RU003950] [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] [A0A077VLD5_STAAU] One of the primary rRNA binding proteins, it binds specifically to the 5'-end of 16S ribosomal RNA.[HAMAP-Rule:MF_01345] [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] [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] [W8USK0_STAAU] Required for dimerization of active 70S ribosomes into 100S ribosomes in stationary phase; 100S ribosomes are translationally inactive and sometimes present during exponential growth.[HAMAP-Rule:MF_00839] [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] [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] [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] [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] [A0A077VHU6_STAAU] 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.[HAMAP-Rule:MF_00480] [W8U8U6_STAAU] 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.[HAMAP-Rule:MF_01315] [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] [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] Publication Abstract from PubMedThe clinical use of the antibiotic erythromycin (ery) is hampered owing to the spread of resistance genes that are mostly mutating rRNA around the ery binding site at the entrance to the protein exit tunnel. Additional effective resistance mechanisms include deletion or insertion mutations in ribosomal protein uL22, which lead to alterations of the exit tunnel shape, located 16 A away from the drug's binding site. We determined the cryo-EM structures of the Staphylococcus aureus 70S ribosome, and its ery bound complex with a two amino acid deletion mutation in its ss hairpin loop, which grants the bacteria resistance to ery. The structures reveal that, although the binding of ery is stable, the movement of the flexible shorter uL22 loop towards the tunnel wall creates a wider path for nascent proteins, thus enabling bypass of the barrier formed by the drug. Moreover, upon drug binding, the tunnel widens further. Exit tunnel modulation as resistance mechanism of S. aureus erythromycin resistant mutant.,Halfon Y, Matzov D, Eyal Z, Bashan A, Zimmerman E, Kjeldgaard J, Ingmer H, Yonath A Sci Rep. 2019 Aug 7;9(1):11460. doi: 10.1038/s41598-019-48019-1. PMID:31391518[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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