Selection of tRNA by the Ribosome Requires a Transition from an Open to a Closed Form

Ogle, J.M.; Murphy, F.V.; Tarry, M.J.; Ramakrishnan, V.

doi:10.1016/s0092-8674(02)01086-3

Cited by 613 publications

(870 citation statements)

References 47 publications

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“…Crystal structures of aminoglycosides bound to the prokaryotic 30S ribosomal subunit (Carter et al 2000;Ogle et al 2001Ogle et al , 2002 and to oligonucleotides containing a minimal 16S rRNA decoding site (Vicens and Westhof 2001, 2003 have shown that aminoglycoside binding (particularly the contacts made by rings I and II) induces A1492 and A1493 to flip out of helix 44 in the absence of cognate aminoacyl-tRNA binding, thus making the ribosome more prone to errors in tRNA selection. Both structural and functional studies indicate that the degree of aminoglycoside binding to the prokaryotic decoding site is greatly influenced by two nonconserved nucleotides, A1408 and G1491.…”

Section: Discussionmentioning

confidence: 99%

Eukaryotic ribosomal RNA determinants of aminoglycoside resistance and their role in translational fidelity

Fan-Minogue¹,

Bedwell²

2007

RNA

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Recent studies of prokaryotic ribosomes have dramatically increased our knowledge of ribosomal RNA (rRNA) structure, functional centers, and their interactions with antibiotics. However, much less is known about how rRNA function differs between prokaryotic and eukaryotic ribosomes. The core decoding sites are identical in yeast and human 18S rRNAs, suggesting that insights obtained in studies with yeast rRNA mutants can provide information about ribosome function in both species. In this study, we examined the importance of key nucleotides of the 18S rRNA decoding site on ribosome function and aminoglycoside susceptibility in Saccharomyces cerevisiae cells expressing homogeneous populations of mutant ribosomes. We found that residues G577, A1755, and A1756 (corresponding to Escherichia coli residues G530, A1492, and A1493, respectively) are essential for cell viability. We also found that residue G1645 (A1408 in E. coli ) and A1754 (G1491 in E. coli ) both make significant and distinct contributions to aminoglycoside resistance. Furthermore, we found that mutations at these residues do not alter the basal level of translational accuracy, but influence both paromomycin-induced misreading of sense codons and readthrough of stop codons. This study represents the most comprehensive mutational analysis of the eukaryotic decoding site to date, and suggests that many fundamental features of decoding site function are conserved between prokaryotes and eukaryotes.

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Section: Discussionmentioning

confidence: 99%

Eukaryotic ribosomal RNA determinants of aminoglycoside resistance and their role in translational fidelity

Fan-Minogue¹,

Bedwell²

2007

RNA

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“…The decoding centre of the ribosome forms a geometrically restricted pocket that accurately selects aminoacyl-tRNA in accordance with mRNA codons positioned in the A-site 25,26 . In bacteria, aminoglycosides antibiotics alter translation accuracy and inhibit tRNA translocation by perturbing the conformation of the decoding centre nucleotides.…”

Section: The Decoding Centrementioning

confidence: 99%

Structural basis for the inhibition of the eukaryotic ribosome

Loubresse

Prokhorova

Holtkamp

et al. 2014

Nature

476

488

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“…1). Protons are generally invisible to X-ray crystallography and cryo-EM 12 , and consequently it has not been possible to unambiguously resolve the identity of WC-like mismatches captured within active sites of polymerases 6,7,15,23 and the ribosome decoding site 9,24 . Moreover, WC-like mismatches are predicted to exist in rapid tautomeric (G enol •T/U⇌G•T enol /U enol ) 25,26 equilibria (Fig.…”

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confidence: 99%

Dynamic basis for dG•dT misincorporation via tautomerization and ionization

Kimsey

Szymanski

Zahurancik

et al. 2018

Nature

134

183

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Tautomeric and anionic Watson-Crick-like mismatches play important roles in replication and translation errors through mechanisms that are not fully understood. Using NMR relaxation dispersion, we resolved a sequence-dependent kinetic network connecting G•T/U wobbles with three distinct Watson-Crick mismatches consisting of two rapidly exchanging tautomeric species (Genol•T/U⇌G•Tenol/Uenol; population <0.4%) and one anionic species (G•T−/U−; population ≈0.001% at neutral pH). Inserting the sequence-dependent tautomerization/ionization step into a minimal kinetic mechanism for correct incorporation during replication following initial nucleotide binding leads to accurate predictions of dG•dT misincorporation probability across different polymerases, pH conditions, and for a chemically modified nucleotide, and provides mechanisms for sequence-dependent misincorporation. Our results indicate that the energetic penalty for tautomerization/ionization accounts for ≈10−2−10−3–fold discrimination against misincorporation, which proceeds primarily via tautomeric dGenol•dT and dG•dTenol with contributions from anionic dG•dT− dominating at pH ≥8.4 or for some mutagenic nucleotides.

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Selection of tRNA by the Ribosome Requires a Transition from an Open to a Closed Form

Cited by 613 publications

References 47 publications

Eukaryotic ribosomal RNA determinants of aminoglycoside resistance and their role in translational fidelity

Eukaryotic ribosomal RNA determinants of aminoglycoside resistance and their role in translational fidelity

Structural basis for the inhibition of the eukaryotic ribosome

Dynamic basis for dG•dT misincorporation via tautomerization and ionization

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