Mechanism of tetracycline resistance by ribosomal protection protein Tet(O)
Open accessAbstract
Tetracycline resistance protein Tet(O), which protects the bacterial ribosome from binding the antibiotic tetracycline, is a translational GTPase with significant similarity in both sequence and structure to the elongation factor EF-G. Here, we present an atomic model of the Tet(O)-bound 70S ribosome based on our cryo-electron microscopic reconstruction at 9.6-Å resolution. This atomic model allowed us to identify the Tet(O)-ribosome binding sites, which involve three characteristic loops in domain 4 of Tet(O). Replacements of the three amino-acid tips of these loops by a single glycine residue result in loss of Tet(O)-mediated tetracycline resistance. On the basis of these findings, the mechanism of Tet(O)-mediated tetracycline resistance can be explained in molecular detail. The bacterial tetracycline resistance protein Tet(O) binds to the ribosome, preventing tetracycline from inhibiting translation. Using cryo-electron microscopic reconstruction, the authors present an atomic model of Tet(O) bound to the 70S ribosome, and reveal how Tet(O) promotes antibiotic resistance.
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Written from the paper’s full text.
TL;DR
Tet(O) protects the bacterial ribosome from tetracycline, and this study presents a 9.6 Å cryo-EM reconstruction of the GDPNP-bound Tet(O)-70S complex with a map-fitted atomic model. The model identifies three domain 4 loops—465, 507, and 438—as key for tetracycline resistance, and mutational tests show that disrupting these loops abolishes or strongly reduces Tet(O) function.
Key findings
- The cryo-EM map of the Tet(O)-70S ribosome complex was determined at 9.6 Å resolution (FSC=0.5), with more than 90% occupancy of Tet(O) in the complex.
- Tet(O) shares 50% sequence similarity with EF-G, allowing homology modeling; its domain 4 loops 465, 507, and 438 insert into the 30S head-platform crevice and span about 30 Å.
- The 507-loop is positioned to clash directly with tetracycline: replacement YSP507-509G caused complete loss of Tet(O) activity, and Y507A caused 83% loss.
- Other loop mutations also impaired resistance: L466A caused 33% inhibition, S472A 76%, LGY466-468G complete inhibition; P438A caused 83% inhibition and 436-438G caused 100% inhibition. Wild-type Tet(O) in BW25993 E. coli had a Tc MIC of 2 μg/ml, versus 0.5 μg/ml for untransformed BW25993.
Methods
- Single-particle cryo-EM of the E. coli 70S ribosome in complex with C. jejuni Tet(O) and GDPNP; 1200 CCD images yielded about 110,000 particles, with about 90,000 manually verified, classified using ML3D and supervised classification, and refined in SPIDER to a final 9.6 Å map.
- Homology modeling of Tet(O) based on the T. thermophilus EF-G crystal structure (PDB 2WRI), followed by molecular dynamics flexible fitting (MDFF) into the cryo-EM map with the 70S ribosome X-ray structure.
- Mutational validation in E. coli BW25993 using plasmid-expressed Tet(O) mutants; MICs measured in 96-well plates, with mutants constructed by overlap extension PCR.
Limitations
- The paper does not include a formal Limitations section. It states that Tet(O)’s structure has not been solved by crystallography, so the atomic model was built by homology to EF-G.
- The reconstruction is at 9.6 Å resolution, and the authors note that the map-fitted structure would need slight adjustment around the GDPNP-binding position if GDPNP were included in the fitted structure.
- The proposed post-release untwisting of helix 18 “must be assumed” as part of ribosomal rescue, indicating that this step is inferred rather than directly observed.
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Claims the paper makes
0 of 39 cited sources checked · 0 supported · 0 flagged
- Findingown data
The sequence alignment results indicate a high sequence similarity of 50% between Tet(O) and EF-G.
“The sequence alignment results indicate a high sequence similarity (50%) between Tet(O) and EF-G, a firm basis for using homology modeling (Supplementary Fig. S2).”
Quote in the paperSubstantial claim - Findingown data
The authors obtained a three-dimensional cryo-EM density map for the complex of Tet(O) bound with the 70S ribosome in the presence of GDPNP at a resolution of 9.6 Å.
“We obtained a three-dimensional cryo-EM density map for the complex of Tet(O) bound with the 70S ribosome in the presence of the nonhydrolyzable GTP analog GDPNP at a resolution of 9.6 Å (FSC=0.5 criterion, Supplementary Fig. S1).”
Quote in the paperSubstantial claim - Findingown data
Classification results indicate a very high occupancy of more than 90% of Tet(O) in the complex with the 70S ribosome.
“The classification results indicate a very high (more than 90%) occupancy of Tet(O) in the complex with the 70S ribosome.”
Quote in the paperNot a substantial claim - Findingown data
On the 50S subunit side, Tet(O) contacts the GTPase-associated center, between residues 619-620 in domain III and nucleotide 1066 in helix 43 of the 23S rRNA.
“On the 50S subunit side, Tet(O) contacts the GTPase-associated center, between residues 619–620 in domain III and nucleotides 1066 in helix 43 of the 23S rRNA.”
Quote in the paperSubstantial claim - Findingown data
The 507-loop and the 438-loop occupy approximately the position where the anticodon stem-loop of an A-site tRNA would occur in a normal translating ribosome.
“The 507-loop and the 438-loop occupy approximately the position where the anticodon stem-loop of an A-site tRNA would occur in a normal translating ribosome, while the 465-loop extends into the structural pocket formed between nucleotides 1055 and 1209 within helix 34 (Figs. 3c).”
Quote in the paperSubstantial claim
- Findingown data
Another Tet(O) binding-induced change in the ribosome occurs at helix 18, including nucleotide 530.
“Another Tet(O) binding-induced change in the ribosome occurs at helix 18, including nucleotide 530, which is crucially involved in the network of bases during the normal decoding process.”
Quote in the paperSubstantial claim - Findingown data
The structure of the 70S-Tet(O) complex in the presence of GDPNP has allowed the authors to visualize the details of binding between the 70S ribosome and Tet(O).
“In this study, the structure of the 70S-Tet(O) complex in the presence of GDPNP has allowed us to visualize the details of binding between the 70S ribosome and Tet(O).”
Quote in the paperSubstantial claim - Findingown data
Point mutation L466A resulted in a 33% inhibition of Tet(O)-mediated resistance.
“A point mutation of the two sites, L466A or S472A, resulted in a 33% and 76% inhibition of Tet(O)-mediated resistance, respectively.”
Quote in the paperSubstantial claim - Findingown data
The 465-loop occupies the position of nucleotide 1209.
“According to the Tc-bound 30S subunit, this loop occupies the position of nt 1209.”
Quote in the paperSubstantial claim - Findingown data
The fitted structure closely captures the conformation of the entire complex as formed in the density map.
“The fitted structure, as shown in Fig. 3, closely captures the conformation of the entire complex as formed in the density map, which allows us to characterize the interactions between Tet(O) and the ribosome in detail.”
Quote in the paperSubstantial claim - Findingown data
Single-point mutation P438A resulted in 83% inhibition of Tet(O) activity.
“A single-point mutation (P438A) and substitution of the three residues 436–438 by a glycine resulted in 83% and 100% inhibition, respectively.”
Quote in the paperSubstantial claim - Findingnone given
The overall ribosome conformation displays no intersubunit rotation when Tet(O) is stalled on the ribosome in the presence of GDPNP.
“The overall ribosome conformation displays no intersubunit rotation when Tet(O) is stalled on the ribosome in the presence of GDPNP.”
Quote in the paperSubstantial claim - Findingnone given
Tet(O) binds with the ribosome on both the 30S and 50S subunits.
“Tet(O) binds with the ribosome on both the 30S and 50S subunits.”
Quote in the paperSubstantial claim - Findingown data
Tet(O) residues 512-513 in the map-fitted structure are within bonding distance from nucleotides 516-519 of helix 18.
“The Tet(O) residue 512–513 in the map-fitted structure are within bonding distance from nucleotides 516–519 of helix 18.”
Quote in the paperSubstantial claim - Findingown data
Residues 358 and 379 in domain III of Tet(O) seem to directly interact with S12's residues 74-76.
“Residues 358 and 379 in domain III of TetO seem to be directly to interact with S12’s residues 74–76.”
Quote in the paperSubstantial claim - Findingown data
The residues of Tet(O) responsible for GTP hydrolysis form a similar structural pocket as in EF-G, which surrounds the sarcin-ricin loop.
“The residues of Tet(O) responsible for GTP hydrolysis form a similar structural pocket as in EF-G, which surrounds the sarcin-ricin loop (nts in the 2662-loop).”
Quote in the paperSubstantial claim - Findingown data
The three loops in domain IV of Tet(O), namely the 465-, 507- and 438-loop, insert into the head-platform crevice, spanning across about 30 Å.
“On the 30S subunit, the three loops in domain IV of Tet(O), namely the 465-, 507- and the 438-loop, insert into the head-platform crevice, spanning across about 30 Å (Figs. 3c–3d).”
Quote in the paperSubstantial claim - Findingown data
The alignment shows that the Tc-interacting loops are differentially conserved between EF-G and Tet families, particularly in the 438- and 507-loop.
“The alignment shows that the Tc-interacting loops are differentially conserved between EF-G and Tet families, particularly in the 438- and 507-loop, which have very different amino acid compositions.”
Quote in the paperNot a substantial claim - Findingown data
In this unusual conformation of helix 18, its nucleotide 530 is also reoriented.
“In this unusual conformation of helix 18, its nucleotide 530 is also reoriented.”
Quote in the paperSubstantial claim - Findingown data
The presence of the 465-loop inside the structural pocket near nucleotides 1051 and 1209 in the 16S rRNA leads to a local distortion of the 16S rRNA in the immediate vicinity of the Tc-binding site.
“The presence of the 465-loop inside the structural pocket near nucleotides 1051 and 1209 in the 16S rRNA leads to a local distortion of the 16S rRNA, in the immediate vicinity of the Tc-binding site (Fig. 3d).”
Quote in the paperSubstantial claim - Findingnone given
The binding of Tc does not change the backbone shape from its shape in the Tc-free ribosome.
“Interestingly, the binding of Tc does not change the backbone shape from its shape in the Tc-free ribosome.”
Quote in the paperNot a substantial claim - Findingown data
Helix 69 of the 23S rRNA is positioned beyond a bonding distance from Tet(O); the closest point (nucleotide 1914) is about 6 Å away from Tet(O).
“Interestingly, helix 69 of the 23S rRNA, which was repeatedly found to be involved in the interactions with other ribosomal factors such as the EF-Tu-aminoacyl-tRNA complex and EF-G 12,19, is positioned beyond a bonding distance from Tet(O). The closest point (nucleotide 1914) is about 6 Å away from Tet(O).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [12] Gao Y. G., Selmer M., Dunham C. M., Weixlbaumer A., Kelley A. C., Ramakrishnan V. The structure of the ribosome with elongation factor G trapped in the posttranslocational state. Science 326, 694–699 (2009). source
Not checked in the free run.
- cites [19] Ogle J. M., Brodersen D. E., Clemons W. M. Jr, Tarry M. J., Carter A. P., Ramakrishnan V. Recognition of cognate transfer RNA by the 30S ribosomal subunit. Science 292, 897–902 (2001). source
Not checked in the free run.
- Findingreasoning
The position of nucleotide 1054 in the current structure is re-oriented from being in the Tc-bound ribosome, otherwise it would clash with the 507-loop in Tet(O).
“The position of nt 1054 in the current structure is re-oriented from being in the Tc-bound ribosome, otherwise it would clash with the 507-loop in Tet(O).”
Quote in the paperSubstantial claim - Findingown data
Point mutation S472A resulted in a 76% inhibition of Tet(O)-mediated resistance.
“A point mutation of the two sites, L466A or S472A, resulted in a 33% and 76% inhibition of Tet(O)-mediated resistance, respectively.”
Quote in the paperSubstantial claim - Findingown data
The model of Tet(O) closely resembles the structural features of EF-G in a 70S ribosome-bound GTP form.
“Our model of Tet(O) closely resembles the structural features of EF-G which is in a 70S ribosome-bound GTP form (Fig. 2).”
Quote in the paperSubstantial claim - Findingown data
In the complex with Tet(O), the backbone shape of helix 34 deviates from the normal structure as formed in the X-ray structures of the 30S subunit either bound or unbound with Tc.
“In the complex with Tet(O), the backbone shape of helix 34 deviates from the normal structure as formed in the X-ray structures of the 30S subunit either bound or unbound with Tc (Fig. 3e).”
Quote in the paperSubstantial claim - Findingown data
This clash is resolved by the re-orientation of nucleotide 516, which appears in a twisted conformation of helix 18 in the map-fitted structure.
“This clash is resolved by the re-orientation of nucleotide 516, which appears in a twisted conformation of helix 18 in our map-fitted structure.”
Quote in the paperSubstantial claim - Findingown data
In the Tet(O) complex, the closest distance is found between nucleotide 2663 and residue 40, about 4 Å.
“In the Tet(O) complex, the closest distance is found to be between nucleotide 2663 and residue 40, about 4 Å.”
Quote in the paperNot a substantial claim - Findingown data
Replacement YSP507-509G resulted in complete loss of Tet(O) activity.
“Replacement YSP507-509G resulted in complete loss of Tet(O) activity, while mutation Y507A resulted in 83% loss of Tet(O) activity.”
Quote in the paperSubstantial claim - Findingown data
Substitution of residues 466-468 by a single glycine (LGY466-468G) resulted in complete inhibition of Tet(O) activity.
“However, substitution of residues 466–468 by a single glycine (LGY466-468G) resulted in complete inhibition of Tet(O) activity.”
Quote in the paperSubstantial claim - Findingown data
Mutation Y507A resulted in 83% loss of Tet(O) activity.
“Replacement YSP507-509G resulted in complete loss of Tet(O) activity, while mutation Y507A resulted in 83% loss of Tet(O) activity.”
Quote in the paperSubstantial claim - Findingown data
The 465-loop extends into the structural pocket formed between nucleotides 1055 and 1209 within helix 34.
“The 507-loop and the 438-loop occupy approximately the position where the anticodon stem-loop of an A-site tRNA would occur in a normal translating ribosome, while the 465-loop extends into the structural pocket formed between nucleotides 1055 and 1209 within helix 34 (Figs. 3c).”
Quote in the paperSubstantial claim - Findingcitation
This ribosome conformation agrees with the X-ray structure of the 70S ribosome bound with EF-G-GDP-fusidic acid.
“This ribosome conformation agrees with the X-ray structure of the 70S ribosome bound with EF-G-GDP-fusidic acid 12.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [12] Gao Y. G., Selmer M., Dunham C. M., Weixlbaumer A., Kelley A. C., Ramakrishnan V. The structure of the ribosome with elongation factor G trapped in the posttranslocational state. Science 326, 694–699 (2009). source
Not checked in the free run.
- Findingown data
Substitution of the three residues 436-438 by a glycine resulted in 100% inhibition of Tet(O) activity.
“A single-point mutation (P438A) and substitution of the three residues 436–438 by a glycine resulted in 83% and 100% inhibition, respectively.”
Quote in the paperSubstantial claim - Premisecitation
The base of nucleotide 1054 plays a crucial role in holding tetracycline on the ribosome.
“The base of nucleotide 1054 in particular seems to play a crucial role in holding tetracycline on the ribosome based on the crystal structure by Ramakrishnan and coworkers (PDB ID 1HNW, 12).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [12] Gao Y. G., Selmer M., Dunham C. M., Weixlbaumer A., Kelley A. C., Ramakrishnan V. The structure of the ribosome with elongation factor G trapped in the posttranslocational state. Science 326, 694–699 (2009). source
Not checked in the free run.
- Premisecitation
Tetracycline binding prevents an entering aminoacyl-tRNA from being recognized by the codon in the mRNA and thereby incapacitates the ribosome for protein synthesis.
“Thus, Tc binding prevents any entering aminoacyl-tRNA from being recognized by the codon in the messenger RNA and thereby incapacitates the ribosome for protein synthesis 3.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [3] Epe B., Woolley P., Hornig H. Competition between tetracycline and tRNA at both P and A sites of the ribosome of Escherichia coli. FEBS Lett. 213, 443–447 (1987). source
Not checked in the free run.
- Premiseown data
Tet(O) protects the bacterial ribosome from binding the antibiotic tetracycline.
“Tetracycline resistance protein Tet(O), which protects the bacterial ribosome from binding the antibiotic tetracycline, is a translational GTPase with significant similarity in both sequence and structure to the elongation factor EF-G.”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [6] Margus T., Remm M., Tenson T. Phylogenetic distribution of translational GTPases in bacteria. BMC Genomics 8, 15 (2007). source
Not checked in the free run.
- cites [7] Burdett V. Tet(M)-promoted release of tetracycline from ribosomes is GTP dependent. J. Bacteriol. 178, 3246–3251 (1996). source
Not checked in the free run.
- cites [8] Connell S. R., Trieber C. A., Dinos G. P., Einfeldt E., Taylor D. E., Nierhaus K. H. Mechanism of Tet(O)-mediated tetracycline resistance. EMBO J. 22, 945–953 (2003). source
Not checked in the free run.
- Premisecitation
The existing 16-Å reconstruction of Tet(O)-70S is unsuitable for building an atomic model.
“The existing 16-Å reconstruction of Tet(O)-70S 9 is unsuitable for this purpose.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [9] Spahn C. M. et al. Localization of the ribosomal protection protein Tet(O) on the ribosome and the mechanism of tetracycline resistance. Mol. Cell. 7, 1037–1045 (2001). source
Not checked in the free run.
- Premisecitation
Tetracycline adheres to the 30S subunit through multiple hydrogen bonds with nucleotide 1054.
“Tetracycline adheres to the 30S subunit through multiple hydrogen bonds with nucleotide 1054.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [12] Gao Y. G., Selmer M., Dunham C. M., Weixlbaumer A., Kelley A. C., Ramakrishnan V. The structure of the ribosome with elongation factor G trapped in the posttranslocational state. Science 326, 694–699 (2009). source
Not checked in the free run.
- Premisecitation
The high degree of sequence homology shared by Tet(O) and EF-G makes it possible to build an atomic model of Tet(O) based on the X-ray structure of EF-G, using a cryo-EM map as constraint, provided its resolution is sufficient.
“The high degree of sequence homology shared by Tet(O) and EF-G 11 makes it possible to build an atomic model of Tet(O) based on the X-ray structure of EF-G, using a cryo-EM map as constraint, provided its resolution is sufficient.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [11] Sanchez-Pescador R., Brown J. T., Roberts M., Urdea M. S. Homology of the TetM with translational elongation factors: implications for potential modes of tetM-conferred tetracycline resistance. Nucleic Acids Res. 16, 1218 (1988). source
Not checked in the free run.
- Premisecitation
The ribosome's effect on the conformation of EF-G is substantial, causing domain IV to be reoriented relative to the other domains.
“The ribosome’s effect on the conformation of EF-G is substantial, as well, causing domain IV to be reoriented relative to the other domains, as shown by cryo-EM 24 and X-ray structures 12 of the ribosome bound with EF-G in the presence of fusidic acid.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [24] Li W., Trabuco L. G., Schulten K., Frank J. Molecular dynamics of EF-G during translocation. Proteins 79, 1478–1486 (2011). source
Not checked in the free run.
- cites [12] Gao Y. G., Selmer M., Dunham C. M., Weixlbaumer A., Kelley A. C., Ramakrishnan V. The structure of the ribosome with elongation factor G trapped in the posttranslocational state. Science 326, 694–699 (2009). source
Not checked in the free run.
- Premisecitation
A contact between the 507-loop of EF-G and the P-site tRNA is essential for the translocation of tRNA.
“In this translocational complex, a contact observed between the 507-loop of EF-G and the P-site tRNA seems to be essential for the translocation of tRNA based on the significant conformational flexibility of this loop 12.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [12] Gao Y. G., Selmer M., Dunham C. M., Weixlbaumer A., Kelley A. C., Ramakrishnan V. The structure of the ribosome with elongation factor G trapped in the posttranslocational state. Science 326, 694–699 (2009). source
Not checked in the free run.
- Premisecitation
In the GDPNP-bound form, Tet(O) was earlier shown biochemically to promote release of Tc from the 70S ribosome.
“In the GDPNP-bound form Tet(O) was earlier shown biochemically to promote release of Tc from the 70S ribosome 20,22, and the elucidation of the current structure therefore provides direct functional insights into the mechanisms of Tet(O)-mediated Tc resistance.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [20] Voorhees R. M., Schmeing T. M., Kelley A. C., Ramakrishnan V. The mechanism for activation of GTP hydrolysis on the ribosome. Science 330, 835–838 (2010). source
Not checked in the free run.
- cites [22] Trieber C. A., Burkhardt N., Nierhaus K. H., Taylor D. E. Ribosomal protection from tetracycline mediated by Tet(O): Tet(O) interaction with ribosomes is GTP-dependent. Biol. Chem. 379, 847–855 (1998). source
Not checked in the free run.
- Premisenone given
Binding with GDPNP allows Tet(O) to remain in its GTP form.
“Essentially, binding with GDPNP allows Tet(O) to remain in its GTP form.”
Quote in the paperSubstantial claim - Interpretationown data
The integrity of the residues identified in the cryo-EM reconstruction as binding sites is crucial for Tet(O) functionality.
“In summary, these results demonstrate that the integrity of the residues identified in our cryo-EM reconstruction as binding sites is crucial for Tet(O) functionality.”
Quote in the paperSubstantial claim - Interpretationreasoning
GTP hydrolysis takes place in this pocket.
“It is in this pocket where the hydrolysis takes place.”
Quote in the paperSubstantial claim - Interpretationcitation
The corridor acts as the only pathway for the dissociating Tc molecule's release from the ribosome.
“The dissociating Tc molecule has to navigate this corridor, which acts as the only pathway for the molecule’s release from the ribosome, which might explain the high activation energy of the process 8.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [8] Connell S. R., Trieber C. A., Dinos G. P., Einfeldt E., Taylor D. E., Nierhaus K. H. Mechanism of Tet(O)-mediated tetracycline resistance. EMBO J. 22, 945–953 (2003). source
Not checked in the free run.
- Interpretationreasoning
The original orientation of helix 18 must be restored if translation on the ribosome were to resume after Tet(O) is released along with Tc.
“Evidently, the original orientation must be restored if translation on the ribosome were to resume after the Tet(O) is released from the ribosome along with Tc.”
Quote in the paperSubstantial claim - Interpretationown data
The 465-loop is responsible for distorting the backbone shape at nucleotides 1051-1054 of 16S rRNA, which weakens or abolishes the binding of Tc at this site with the RNA.
“By combining structural and mutational analyses, the present study provides structural insights into how the three loops in domain IV (see Fig. 3) might cooperate to expel Tc from the ribosome: the 465-loop is responsible for distorting the backbone shape at nucleotides 1051–1054 of 16S rRNA, which weakens or abolishes the binding of Tc at this site with the RNA;”
Quote in the paperSubstantial claim - Interpretationnone given
Although the 465-loop is placed outside the decoding center at the A site, it apparently plays a role in restraining the structural flexibility between the 1055 and 1029 ends.
“Although this third loop is placed outside the decoding center at the A site, it apparently plays a role in restraining the structural flexibility between the 1055 and 1029 ends.”
Quote in the paperSubstantial claim - Interpretationcitation
The interaction between S12 and Tet(O) at multiple sites is similar to the bridge-like connection that S12 forms with two sites of the A/T-site tRNA in the EF-Tu-tRNA complex.
“This interaction between S12 and Tet(O) at multiple sites is similar to the bridge-like connection that S12 forms with two sites of the A/T-site tRNA in the EF-Tu-tRNA complex, as previously described for the X-ray structure of the ternary complex-bound ribosome complex 19.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [19] Ogle J. M., Brodersen D. E., Clemons W. M. Jr, Tarry M. J., Carter A. P., Ramakrishnan V. Recognition of cognate transfer RNA by the 30S ribosomal subunit. Science 292, 897–902 (2001). source
Not checked in the free run.
- Interpretationreasoning
In the presence of Tc, a primary portion of the space for the anticodon loop is already occupied by Tc, which causes a decisive rejection of the aminoacyl-tRNA from the ribosome before codon-anticodon recognition can take place.
“In the presence of Tc, a primary portion of the space for the anticodon loop is already occupied by Tc (Fig. 3e) which causes a decisive rejection of the aminoacyl-tRNA from the ribosome before codon-anticodon recognition can take place.”
Quote in the paperSubstantial claim - Interpretationcitation
The presence of the 465-loop of Tet(O) at the base of the 30S subunit's beak prevents the head of the 30S subunit from rotating, a motion required in the normal course of mRNA-tRNA translocation.
“The presence of the 465-loop of Tet(O) at the base of the 30S subunit’s beak prevents the head of the 30S subunit from rotating, a motion required in the normal course of mRNA-tRNA translocation 9.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [9] Spahn C. M. et al. Localization of the ribosomal protection protein Tet(O) on the ribosome and the mechanism of tetracycline resistance. Mol. Cell. 7, 1037–1045 (2001). source
Not checked in the free run.
- Interpretationreasoning
The 507-loop appears to have the most direct and most crucial role in bestowing tetracycline resistance.
“The 507-loop, which is located in the middle of the lined-up three loops, appears to have the most direct, and most crucial role in bestowing tetracycline resistance as evident from its position relative to Tc.”
Quote in the paperSubstantial claim - Interpretationreasoning
When Tet(O) enters into the Tc-bound ribosome, the 507-loop cannot be settled into the ribosome complex because Tc already occupies the close vicinity of nucleotide 1054 and forms multiple hydrogen bonds with the ribosome.
“When Tet(O) enters into the Tc-bound ribosome, the 507-loop cannot be settled into the ribosome complex because Tc already occupies the close vicinity of nucleotide 1054 and forms multiple hydrogen bonds with the ribosome.”
Quote in the paperSubstantial claim - Interpretationown data
In the current Tet(O)-ribosome complex, helix 69 has no direct involvement.
“Therefore, in the current Tet(O)-ribosome complex, helix 69 has no direct involvement.”
Quote in the paperNot a substantial claim - Interpretationown data
The 438-loop and nucleotides around 966 and 1196 of the 16S rRNA with their surrounding nucleotides form a corridor that starts at the position of Tc and leads to the outside of the ribosome.
“We observe that this loop and nucleotides around 966 and 1196 of the 16S rRNA with their surrounding nucleotides form a corridor, which starts at the position of Tc and leads to the outside of the ribosome (Fig. 3f).”
Quote in the paperSubstantial claim - Interpretationreasoning
The competition for the same site guarantees that Tet(O) and Tc cannot coexist in the ribosomal complex.
“The competition for the same site guarantees that Tet(O) and Tc cannot coexist in the ribosomal complex.”
Quote in the paperSubstantial claim - Interpretationreasoning
The subsequent untwisting process indicates a substantial flexibility of the structure of helix 18.
“This subsequent untwisting process, which we must assume as part of the bacterial rescue of the ribosome, indicates a substantial flexibility of the structure of helix 18.”
Quote in the paperNot a substantial claim- The authors state this as an assumption: The untwisting of helix 18 and restoration of the original orientation occur spontaneously after Tet(O) release as part of the bacterial rescue of the ribosome.
- Interpretationreasoning
The contacts between Tet(O) and the ribosome seem to collectively play the role of preventing or reversing the binding of Tc to the ribosome.
“These contacts between the Tet(O) and the ribosome seem to collectively play the role of preventing or reversing the binding of Tc to the ribosome”
Quote in the paperSubstantial claim - Study design and conductown data
The mutation results are fully consistent with the cryo-EM structural analysis.
“The mutation results are fully consistent with our cryo-EM structural analysis.”
Quote in the paperSubstantial claim - Interpretationown data
The sequence conservation pattern suggests that a certain amount of sequence variation is tolerated in the loops while functionality is maintained.
“This suggests that a certain amount of sequence variation is tolerated in the loops, while functionality is maintained.”
Quote in the paperNot a substantial claim - Interpretationown data
These results indicate crucial importance of the 507-loop for Tet(O)'s ability to protect the ribosome from Tc.
“These results indicate crucial importance of the 507-loop for the Tet(O)’s ability to protect the ribosome from Tc.”
Quote in the paperSubstantial claim - Interpretationreasoning
Following the positional change in nucleotide 1209, the backbone shape of the fragment around nucleotide 1051 must adjust.
“Following the positional change in nucleotide 1209, the backbone shape of the fragment around nt 1051 also must adjust.”
Quote in the paperSubstantial claim - Interpretationreasoning
The structural similarity of Tet(O) to EF-G suggests structural flexibility in the equivalently positioned loops of Tet(O).
“The structural similarity of Tet(O) to EF-G suggests structural flexibility in the equivalently positioned loops of Tet(O).”
Quote in the paperSubstantial claim - Interpretationown data
These results, combined with the structural data, verify the importance of the proposed corridor for Tc's release from the ribosome.
“These results, combined with our structural data, verify the importance of our proposed corridor for Tc’s release from the ribosome (see Discussion).”
Quote in the paperSubstantial claim - Interpretationown data
These results suggest that the residues in the 465-loop collectively play an important role in Tet(O)'s function.
“These results suggest that the residues in the 465-loop collectively play an important role in the Tet(O)’s function, even though sequence variation is tolerated in the loops, again as predicted from the position of this loop in the model and the conservation analysis.”
Quote in the paperSubstantial claim - Interpretationreasoning
The most direct effect of Tet(O) binding in preventing Tc from binding to the 30S subunit seems to be the result of a competition between residues 507-509 of Tet(O) and Tc for the same space.
“The most direct effect of Tet(O) binding in preventing Tc from binding to the 30S subunit seems to be the result of a competition between residues 507–509 of Tet(O) and Tc for the same space.”
Quote in the paperSubstantial claim - Interpretationcitation
The corridor might explain the high activation energy of the Tc release process.
“The dissociating Tc molecule has to navigate this corridor, which acts as the only pathway for the molecule’s release from the ribosome, which might explain the high activation energy of the process 8.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [8] Connell S. R., Trieber C. A., Dinos G. P., Einfeldt E., Taylor D. E., Nierhaus K. H. Mechanism of Tet(O)-mediated tetracycline resistance. EMBO J. 22, 945–953 (2003). source
Not checked in the free run.
- Interpretationnone given
The 438-loop along with nucleotide 966 and 1196 should form a corridor allowing Tc to exit.
“and the 438-loop along with nucleotide 966 and 1196 should form a corridor allowing Tc to exit.”
Quote in the paperNot a substantial claim - Interpretationreasoning
The 507-loop in the middle of the three loops directly pushes Tc out of the ribosome.
“the 507-loop in the middle of these three directly pushes Tc out of the ribosome;”
Quote in the paperSubstantial claim
- May combine two claims. 25
- Classified as probably not a substantial claim. 5
May combine two claims.
Findingown dataIn all the sequences, the highly conserved nucleotide-binding motifs are perfectly aligned, and the sequence of Tet(O) is divided into five domains corresponding to the domains defined by the sequence of EF-G.
“In all these sequences, the highly conserved nucleotide-binding motifs are perfectly aligned, and the sequence of Tet(O) is divided into five domains, corresponding to the domains defined by the sequence of EF-G.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe density for Tet(O) in the improved map is at a position that agrees with the earlier study, but its boundary and shape are better defined in the context of the 70S ribosome.
“The density for Tet(O) in this improved map is at a position which agrees with that described in the earlier study 9, but boundary and shape are better defined in the context with the 70S ribosome (Fig. 1).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [9] Spahn C. M. et al. Localization of the ribosomal protection protein Tet(O) on the ribosome and the mechanism of tetracycline resistance. Mol. Cell. 7, 1037–1045 (2001). source
Not checked in the free run.
May combine two claims.
Findingown dataThe improved resolution of the density map allowed the authors to build an atomic model of Tet(O), guided by its homology to EF-G, and to characterize its binding interactions with the ribosome.
“In the present study, the improved resolution of the density map allowed us to build an atomic model of Tet(O), guided by its homology to EF-G, and characterize its binding interactions with the ribosome.”
Quote in the paperSubstantial claimMay combine two claims.
FindingcitationThe 438-loop is not involved in interactions with Tc and is located about 15 Å away from Tc, but residue 437 is located in the near vicinity of nucleotides 1492-1493 in the 16S rRNA.
“Unlike the 507-loop, the 438-loop is not involved in the interactions with Tc, located about 15 Å away from Tc, but residue 437 is located in the near vicinity of nucleotides 1492–1493 in the 16S rRNA, where the decoding interaction network is observed in a normal translation ribosome 21.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [21] Connell S. R., Trieber C. A., Stelzl U., Einfeldt E., Taylor D. E., Nierhaus K. H. The tetracycline resistance protein Tet(o) perturbs the conformation of the ribosomal decoding centre. Mol. Microbiol. 45, 1463–1472 (2002). source
Not checked in the free run.
May combine two claims.
Findingnone givenS12 residues 483 and 517 are located at the base of the 507- and 465-loops of Tet(O), respectively.
“The S12 residues 483 and 517 are located at the base of the 507- and 465-loops of Tet(O), respectively.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataAs a reference, BW25993 E. coli transformed with plasmid-expressed wild-type Tet(O) had a Tc MIC of 2 μg/ml, and untransformed BW25993 E. coli had an MIC of 0.5 μg/ml.
“As a reference we used BW25993 E. coli strain transformed with a plasmid-expressed wild-type Tet(O), with a Tc MIC of 2 μg/ml and un-transformed BW25993 E. coli, MIC 0.5 μg/ml.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataTet(O) interacts with the 30S subunit protein S12 closely at domain III, and possibly at domain IV.
“Tet(O) interacts with the 30S subunit protein S12 closely at domain III, and possibly at domain IV of Tet(O) (Fig. 3g).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe Tet(O) 438-loop is located close to the mRNA around the A-site codon, with the point of closest approach within 3 Å occurring between residue 438 and the second nucleotide for the A-site codon.
“It is worth noting that the Tet(O) 438-loop is located close to the mRNA around the A-site codon, as shown in our map-fitted structure. The point of closest approach (within 3Å) occurs between residue 438 and the second nucleotide for the A-site codon.”
Quote in the paperSubstantial claimMay combine two claims.
FindingcitationThe bases of nucleotides 1492-1493 in the 16S rRNA flip out toward the Tet(O) 438-loop; this flipped-out conformation was also observed when codon-anticodon recognition takes place in a translating ribosome.
“In addition, the bases of nts 1492–1493 in the 16S rRNA flip out toward the Tet(O)’s 438-loop (Fig. 3); the flipped-out conformation that was also observed when a codon-anticodon recognition takes place in a translating ribosome 21.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [21] Connell S. R., Trieber C. A., Stelzl U., Einfeldt E., Taylor D. E., Nierhaus K. H. The tetracycline resistance protein Tet(o) perturbs the conformation of the ribosomal decoding centre. Mol. Microbiol. 45, 1463–1472 (2002). source
Not checked in the free run.
May combine two claims.
Findingown dataThe loops are not very strongly conserved within the entire Tet family; only 2 out of 6, 6 out of 11 and 4 out of 8 residues are conserved at >60% in the 438-, 465- and 507-loops, respectively.
“However, these loops are not very strongly conserved within the entire Tet family; only 2 out of 6, 6 out of 11 and 4 out of 8 residues are conserved at >60% in the 438-, 465- and 507-loops, respectively (Figs. 4a–b).”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationTet(O) shares five structural domains with EF-G; the first two contain the GTP-binding site and are close to the GTP-associated center of the 50S subunit, while the other three are distinct for Tet(O) and associated with its specific functions.
“Sequence homology shows that Tet(O) shares the five structural domains with EF-G, the first two containing the GTP-binding site and being close to the GTP-associated center of the 50S ribosomal subunit, while the other three domains are distinct for Tet(O) and associated with its specific functions 9,10.”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [9] Spahn C. M. et al. Localization of the ribosomal protection protein Tet(O) on the ribosome and the mechanism of tetracycline resistance. Mol. Cell. 7, 1037–1045 (2001). source
Not checked in the free run.
- cites [10] Thakor N. S., Nechifor R., Scott P. G., Keelan M., Taylor D. E., Wilson K. S. Chimeras of bacterial translation factors Tet(O) and EF-G. FEBS Lett. 582, 1386–1390 (2008). source
Not checked in the free run.
Classified as probably not a substantial claim. May combine two claims.
PremisecitationA previous 16 Å cryo-EM study showed that Tet(O) has a similar shape to EF-G and binds to the same general site within the intersubunit cavity of the ribosome.
“A previous Tet(O) cryo-EM study 9, with a density map at a resolution of 16 Å, allowed the visualization of Tet(O) bound to the Escherichia coli ribosome, revealing that Tet(O) indeed has a similar shape as EF-G and binds to the same general site within the intersubunit cavity of the ribosome.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [9] Spahn C. M. et al. Localization of the ribosomal protection protein Tet(O) on the ribosome and the mechanism of tetracycline resistance. Mol. Cell. 7, 1037–1045 (2001). source
Not checked in the free run.
May combine two claims.
PremisecitationTetracycline targets the small ribosomal subunit, with its primary high-affinity binding site beneath helix 34 of the 16S rRNA in a crevice between the head and platform of the 30S subunit near the A-site codon.
“It targets the small subunit of the bacterial ribosome 2, with the primary high-affinity binding site located beneath helix 34 of the 16S rRNA, in a crevice between the head and platform of the 30S subunit, in close vicinity of the A-site codon 2.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [2] Brodersen D. E., Clemons W. M. Jr., Carter A. P., Morgan-Warren R. J., Wimberly B. T., Ramakrishnan V. The structural basis for the action of the antibiotics tetracycline, pactamycin, and hygromycin B on the 30S ribosomal subunit. Cell 103, 1143–1154 (2000). source
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationThe antibiotic fusidic acid traps EF-G in a conformational intermediate between the GTP and GDP forms.
“The antibiotic fusidic acid traps EF-G in a conformational intermediate between the GTP and GDP forms.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [12] Gao Y. G., Selmer M., Dunham C. M., Weixlbaumer A., Kelley A. C., Ramakrishnan V. The structure of the ribosome with elongation factor G trapped in the posttranslocational state. Science 326, 694–699 (2009). source
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationGTP hydrolysis induces substantial conformational changes in the ribosome.
“It is known that GTP hydrolysis induces substantial conformational changes in the ribosome.”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [23] Fei J., Kosuri P., MacDougall D. D., Gonzalez R. L. Jr Coupling of ribosomal L1 stalk and tRNA dynamics during translation elongation. Mol. Cell. 30, 348–359 (2008). source
Not checked in the free run.
- cites [24] Li W., Trabuco L. G., Schulten K., Frank J. Molecular dynamics of EF-G during translocation. Proteins 79, 1478–1486 (2011). source
Not checked in the free run.
- cites [25] Taylor D. J., Nilsson J., Merrill A. R., Andersen G. R., Nissen P., Frank J. Structures of modified eEF2 80S ribosome complexes reveal the role of GTP hydrolysis in translocation. EMBO J. 26, 2421–2431 (2007). source
Not checked in the free run.
May combine two claims.
PremisecitationTet(O) is a translational GTPase with significant sequence and structural similarity to EF-G.
“Tetracycline resistance protein Tet(O), which protects the bacterial ribosome from binding the antibiotic tetracycline, is a translational GTPase with significant similarity in both sequence and structure to the elongation factor EF-G.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [6] Margus T., Remm M., Tenson T. Phylogenetic distribution of translational GTPases in bacteria. BMC Genomics 8, 15 (2007). source
Not checked in the free run.
- cites [11] Sanchez-Pescador R., Brown J. T., Roberts M., Urdea M. S. Homology of the TetM with translational elongation factors: implications for potential modes of tetM-conferred tetracycline resistance. Nucleic Acids Res. 16, 1218 (1988). source
Not checked in the free run.
May combine two claims.
PremisecitationTet(M) and Tet(O) are paralogs of the translational GTPase EF-G and actively remove Tc from the ribosome in a GTP-hydrolysis-dependent fashion.
“Several of these proteins–the best-known being Tet(M) and Tet(O) – are paralogs of the translational GTPase EF-G 6 and actively remove Tc from the ribosome in a GTP-hydrolysis-dependent fashion 7,8.”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [6] Margus T., Remm M., Tenson T. Phylogenetic distribution of translational GTPases in bacteria. BMC Genomics 8, 15 (2007). source
Not checked in the free run.
- cites [7] Burdett V. Tet(M)-promoted release of tetracycline from ribosomes is GTP dependent. J. Bacteriol. 178, 3246–3251 (1996). source
Not checked in the free run.
- cites [8] Connell S. R., Trieber C. A., Dinos G. P., Einfeldt E., Taylor D. E., Nierhaus K. H. Mechanism of Tet(O)-mediated tetracycline resistance. EMBO J. 22, 945–953 (2003). source
Not checked in the free run.
May combine two claims.
InterpretationreasoningTet(O) enters the ribosome with less demand for space in that region than the anticodon loop of the tRNA; the available space provides an opportunity for Tet(O) to be admitted to the factor binding site.
“In contrast, Tet(O) enters the ribosome with less demand for space in that region than the anticodon loop of the tRNA; the available space provides an opportunity for Tet(O) to be admitted to the factor binding site, important for subsequence GTP hydrolysis.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningWith this disrupted backbone structure, the nucleotides involved in binding with Tc are reoriented, and thus Tc loses its bonds with the ribosome.
“With this disrupted backbone structure, the nucleotides involved in binding with Tc are reoriented, and thus, Tc loses its bonds with the ribosome.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataThe 30S subunit-Tet(O) contact sites identified in the present study can be divided into two categories: those which lead to a clash with the space for the binding of Tc via the 507-loop, and those which disrupt the structure of the 16S rRNA around the Tc-binding site via the 465-loop toward nucleotide 1209 in 16S rRNA.
“The 30S subunit-Tet(O) contact sites we have identified in the present study can be divided into two categories: (1) those which lead to a clash with the space for the binding of Tc via the 507-loop and (2) those which disrupt the structure of the 16S rRNA around the Tc-binding site via the 465-loop toward nucleotide 1209 in 16S rRNA.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataResidue 507 in domain IV and nucleotide 1054 in helix 34 would spatially clash if the fragment of helix 34 remained in its normal position; therefore, the binding of Tet(O) causes a change in that region of backbone.
“Our structure shows that residue 507 in domain IV and nucleotide 1054 in helix 34 would spatially clash if the fragment of helix 34 remained in its normal position. Therefore, the binding of Tet(O) clearly causes a change in that region of backbone.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenThe current map-fitted structure would need to be slightly adjusted around the GDPNP-binding position if GDPNP was included in the fitted structure.
“The current map-fitted structure would need to be slightly adjusted around the GDPNP-binding position if GDPNP was included in the fitted structure.”
Quote in the paperNot a substantial claimMay combine two claims.
Study design and conductown dataThe fitting structure was validated by using a different crystal structure of the 70S ribosome as the starting structure for MDFF; the RMSD of the two 70S ribosomal structures is 1.5 Å, and 1.7 Å for all atoms of Tet(O).
“We validated the fitting structure by using a different crystal structure of the 70S ribosome as the starting structure for the MDFF (2WRI, 2WIJ). The resultant structure of Tet(O) as well as the bases re-arrangement in the 16S rRNA are in good agreement with the model presented in the ms. The RMSD of the two 70S ribosomal structures is just 1.5 Å, and just 1.7 Å for all atoms of Tet(O).”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningThe unpaired nucleotides in helix 34 naturally provide structural flexibility, which is evidently exploited in the binding of Tet(O) to the ribosome.
“These unpaired nucleotides naturally provide structural flexibility, which is evidently exploited in the binding of Tet(O) to the ribosome.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationcitationThe position of Tc in the 30S subunit, mapped to the current structure, would result in a spatial clash between residues 507-509 and Tc if both were present in the same complex; either Tc or the Tet(O) 507-loop would exclusively occupy the same space.
“This position would result in a spatial clash between residues 507–509 and Tc if both were present in the same complex, i.e., either Tc or the Tet(O)’s 507-loop would exclusively occupy the same space.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [2] Brodersen D. E., Clemons W. M. Jr., Carter A. P., Morgan-Warren R. J., Wimberly B. T., Ramakrishnan V. The structural basis for the action of the antibiotics tetracycline, pactamycin, and hygromycin B on the 30S ribosomal subunit. Cell 103, 1143–1154 (2000). source
Not checked in the free run.
Probably not a substantial claim: may not pass S4 (based).
InterpretationreasoningGTP hydrolysis in Tet(O) results in extensive conformational changes in the distal loops of domain IV, particularly in the three flexible loops.
“Accordingly, we predict that GTP hydrolysis in Tet(O) results in extensive conformational changes in the distal loops of domain IV, particularly in the three flexible loops.”
Quote in the paperNot a substantial claimMay combine two claims.
Study design and conductown dataThese results agree with the structural model based on the cryo-EM study, as well as an earlier mutational study of the 507-loop.
“These results agree with the structural model based on our cryo-EM study, as well as an earlier mutational study of the 507-loop 10.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [10] Thakor N. S., Nechifor R., Scott P. G., Keelan M., Taylor D. E., Wilson K. S. Chimeras of bacterial translation factors Tet(O) and EF-G. FEBS Lett. 582, 1386–1390 (2008). source
Not checked in the free run.
May combine two claims.
Interpretationown dataBinding of Tet(O) disrupts the ribosome structure and reshapes the geometry of the backbone where Tc is anchored.
“In addition, binding of Tet(O) disrupts the ribosome structure and reshapes the geometry of the backbone where Tc is anchored (Fig. 3e).”
Quote in the paperSubstantial claimMay combine two claims.
Study design and conductreasoningThe results agree with the results by Wilson and coworkers in all essential details, as expected based on the high sequence homology between Tet(O) and Tet(M).
“Our results agree with the results by Wilson and coworkers in all essential details, as expected based on the high sequence homology between Tet(O) and Tet(M).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [26] Dönhöfer A., Franckenberg S., Wickles S., Berninghausen O., Beckmann R., Wilson D. N. Structural basis for TetM-mediated tetracycline resistance. Proc. Natl Acad. Sci. USA 109, 16900–16905 (2012). source
Not checked in the free run.
The authors state this as an assumption.
The untwisting of helix 18 and restoration of the original orientation occur spontaneously after Tet(O) release as part of the bacterial rescue of the ribosome.
“This subsequent untwisting process, which we must assume as part of the bacterial rescue of the ribosome, indicates a substantial flexibility of the structure of helix 18.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
TetO competes with tetracycline for the same ribosomal space and alters the geometry of the antibiotic binding site, displacing the molecule from the ribosome and allowing protein synthesis to resume.
“Similarly, TetO has also been shown to compete with tetracycline for the same ribosomal space and to alter the geometry of the binding site of the antibiotic, displacing the molecule from the ribosome and allowing protein synthesis to resume (53).”
From Mechanisms of Antibiotic Resistance (2016) · cites this paper as [53]
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Microbial Resistance Mechanisms and Potential of Metal-Organic Framework in Mitigation Thereof
Polash, S. A., Váradi, L., & Shukla, R. (2022) · Nanotechnology in the life sciences · doi:10.1007/978-3-031-10220-2_7 · Cited by 2 · see citing works
Mechanism of Antibiotic Resistance and Pathogenicity of Vibrio cholerae
Saha, S., & Singh, D. V. (2020) · Springer eBooks · doi:10.1007/978-981-15-1695-5_15 · Cited by 2 · see citing works
A tetRA -based promoter system for the generation of conditional knockouts in Campylobacter jejuniPreprint
Cohen, E. J., Quek, R. T., & Beeby, M. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/616649 · Cited by 2 · see citing works
- Authors
- Li, W., Atkinson, G. C., Thakor, N. S., Allas, Ü., Lu, C.-C., Chan, K.-Y., Tenson, T., Schulten, K., Wilson, K. S., Hauryliuk, V., & Frank, J.
- Affiliations
- Columbia University (US)
- University of Tartu (EE)
- University of Ottawa (CA)
- Peking University (CN)
- University of Illinois Urbana-Champaign (US)
- Oklahoma State University (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Frank, Joachim
- Venue
- Nature Communications
- Published
- 2013-02-12
- Volume
- 4
- Issue
- 1
- Pages
- 1477-1477
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC3576927
- OpenAlex
- W1988702718
- Semantic Scholar
- 1d6a04d738d4e9af40c59fe0fce20e059329d858
- Cited by
- 147
- References
- 40
- Citations by year
- 2026: 9 · 2025: 23 · 2024: 10 · 2023: 6 · 2022: 9 · 2021: 17 · 2020: 20 · 2019: 12 · 2018: 14 · 2017: 6 · 2016: 9 · 2015: 4 · 2014: 6 · 2013: 2
- FWCI
- 3.13
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- SHAREOK (University of Oklahoma; Oklahoma State University; Central Oklahoma University) (submittedVersion, other-oa)
- Funders
- National Science Foundation (MCA93S028, 0822613)
- Howard Hughes Medical Institute
- Eesti Teadusfondi (MJD99)
- National Institutes of Health (NIH-R01, MCA93S028, RR005969)
- U.S. Public Health Service (R01 55440)
- Canadian Institutes of Health Research
- European Regional Development Fund
- National Institute of General Medical Sciences (R01GM029169, R01GM055440)
- National Center for Research Resources (P41RR005969)
- European Social Fund
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- tetO, tetracycline resistance, 70S ribosome, translational GTPases, ribosome binding site, antibiotic resistance mechanisms
- MeSH terms
- Amino Acid Sequence, Bacterial Proteins, Carrier Proteins, Guanosine Triphosphate, Models, Molecular, Molecular Sequence Data, Protein Binding, Ribosomal Proteins, Ribosomes, RNA, Transfer, Tetracycline Resistance, Campylobacter jejuni, Protein Structure, Secondary, Protein Structure, Tertiary, Cryoelectron Microscopy, Structural Homology, Protein, Mutant Proteins, Ribosome Subunits, Small, Bacterial, Ribosome Subunits, Large, Bacterial
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