Selection of tRNA by the Ribosome Requires a Transition from an Open to a Closed Form
Open accessAbstract
A structural and mechanistic explanation for the selection of tRNAs by the ribosome has been elusive. Here, we report crystal structures of the 30S ribosomal subunit with codon and near-cognate tRNA anticodon stem loops bound at the decoding center and compare affinities of equivalent complexes in solution. In ribosomal interactions with near-cognate tRNA, deviation from Watson-Crick geometry results in uncompensated desolvation of hydrogen-bonding partners at the codon-anticodon minor groove. As a result, the transition to a closed form of the 30S induced by cognate tRNA is unfavorable for near-cognate tRNA unless paromomycin induces part of the rearrangement. We conclude that stabilization of a closed 30S conformation is required for tRNA selection, and thereby structurally rationalize much previous data on translational fidelity.
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Tetracycline bound at the secondary/Tet-5 sites could exert its inhibitory effect by interfering with the transition between the open and closed states of the 30S ribosomal subunit, which is important for the decoding reaction.
“In this position, tetracycline cannot directly interfere with tRNA binding, but rather, it could exert its inhibitory effect by interfering with the transition between the open and closed states of the 30S ribosomal subunit, which is important for the decoding reaction (34).”
From Ribosomal Protection Proteins and Their Mechanism ofTetracyclineResistance (2003) · cites this paper as [34]
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- Authors
- Ogle, J. M., Murphy, F. V., Tarry, M. J., & Ramakrishnan, V.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- Corresponding author
- Ramakrishnan, V.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2002-11
- Volume
- 111
- Issue
- 5
- Pages
- 721-732
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2126780661
- Cited by
- 663
- References
- 55
- Citations by year
- 2026: 10 · 2025: 17 · 2024: 16 · 2023: 18 · 2022: 16 · 2021: 15 · 2020: 16 · 2019: 27 · 2018: 28 · 2017: 29 · 2016: 27 · 2015: 24 · 2014: 33 · 2013: 33 · 2012: 17
- FWCI
- 12.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 3911 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01gm044973-14)
- National Institute of General Medical Sciences (GM 44973)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- tRNA selection, 30S ribosomal subunit, codon-anticodon pairing, near-cognate tRNA, decoding center, anticodon stem-loop, desolvation, paromomycin, translation fidelity, crystal structure
- MeSH terms
- Anti-Bacterial Agents, Anticodon, Binding, Competitive, Codon, Hydrogen Bonding, Models, Molecular, Nucleic Acid Conformation, Paromomycin, Ribosomes, RNA, Bacterial, RNA, Ribosomal, 16S, RNA, Transfer, RNA, Transfer, Phe, Structure-Activity Relationship, Thermodynamics, Thermus thermophilus, Crystallography, X-Ray, Base Pairing
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