The Structure of the Ribosome with Elongation Factor G Trapped in the Posttranslocational State
Open accessAbstract
Ribosomes Caught in Translation: To synthesize proteins, the ribosome must select cognate transfer RNAs (tRNAs) based on base-pairing with the messenger RNA (mRNA) template (a process known as decoding), form a peptide bond, and then move the mRNA:tRNA assembly relative to the ribosome (a process known as translocation). Decoding and translocation require protein guanosine triphosphatases (GTPases), and, while high-resolution structures of the ribosome have greatly furthered our understanding of ribosome function, the detailed mechanism of these GTPases during the elongation cycle remains unclear. Two Research Articles now give a clearer view of these steps in bacterial protein synthesis (see the Perspective by Liljas ). Schmeing et al. (p. 688 , published online 15 October) present the crystal structure of the ribosome bound to Elongation factor-Tu (EF-Tu) and amino-acyl tRNA that gives insight into how EF-Tu contributes to accurate decoding. Gao et al. (p. 694 , published online 15 October) describe the crystal structure of the ribosome bound to Elongation factor-G (EF-G) trapped in a posttranslocation state by the antibiotic fusidic acid that gives insight into how EF-G functions in translocation.
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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.”
From Mechanism of tetracycline resistance by ribosomal protection protein Tet(O) (2013) · cites this paper as [12]
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.”
From Mechanism of tetracycline resistance by ribosomal protection protein Tet(O) (2013) · cites this paper as [12]
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.”
From Mechanism of tetracycline resistance by ribosomal protection protein Tet(O) (2013) · cites this paper as [12]
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).”
From Mechanism of tetracycline resistance by ribosomal protection protein Tet(O) (2013) · cites this paper as [12]
The 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.”
From Mechanism of tetracycline resistance by ribosomal protection protein Tet(O) (2013) · cites this paper as [12]
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.”
From Mechanism of tetracycline resistance by ribosomal protection protein Tet(O) (2013) · cites this paper as [12]
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).”
From Mechanism of tetracycline resistance by ribosomal protection protein Tet(O) (2013) · cites this paper as [12]
The proline-rich loop I of TetM is bent significantly to allow interaction with the RPP-specific C-terminal helix-αA CTE, whereas loop I of EF-G is longer and adopts an extended conformation on the ribosome that establishes interaction with the P-tRNA.
“The proline-rich loop I, located between β2 4 and β3 4 , is bent significantly to allow interaction with the RPP-specific C-terminal helix-αA CTE (SI Appendix, Fig. S8A), whereas, in contrast, loop I of EF-G is longer and adopts an extended conformation on the ribosome that establishes interaction with the P-tRNA (22) (SI Appendix, Fig. S8B).”
From Structural basis for TetM-mediated tetracycline resistance (2012) · cites this paper as [22]
EF-G is shifted in position relative to TetM, being located closer to the 30S subunit and further away from the stalk base of the 50S subunit.
“whereas the overall orientation of TetM on the ribosome is similar to that of EF-G (22), EF-G is shifted in position relative to TetM, being located closer to the 30S subunit and further away from the stalk base of the 50S subunit (Fig. 1D and SI Appendix, Fig. S6).”
From Structural basis for TetM-mediated tetracycline resistance (2012) · cites this paper as [22]
TetM significantly overlaps with the anticodon stem-loop of the A-tRNA.
“TetM significantly overlaps with the anticodon stem-loop of the A-tRNA (Fig. 1C), as observed for EF-G bound to a posttranslocation state ribosome (22).”
From Structural basis for TetM-mediated tetracycline resistance (2012) · cites this paper as [22]
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- Authors
- Gao, Y.-G., Selmer, M., Dunham, C. M., Weixlbaumer, A., Kelley, A. C., & Ramakrishnan, V.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- Corresponding author
- Selmer, Maria
- Dunham, Christine M.
- Weixlbaumer, Albert
- Ramakrishnan, V.
- Venue
- Science
- Published
- 2009-10-30
- Volume
- 326
- Issue
- 5953
- Pages
- 694-699
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3763468
- OpenAlex
- W1992657741
- Cited by
- 513
- References
- 45
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 15 · 2023: 13 · 2022: 20 · 2021: 27 · 2020: 23 · 2019: 23 · 2018: 18 · 2017: 23 · 2016: 35 · 2015: 40 · 2014: 42 · 2013: 54 · 2012: 56
- FWCI
- 21.76
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DORA PSI (Paul Scherrer Institute) (submittedVersion)
- Funders
- Wellcome Trust (082086)
- 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
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Keywords
- ribosome structure, elongation factor G, translocation, decoding, elongation factor Tu, aminoacyl-tRNA, fusidic acid, protein synthesis, crystal structure
- MeSH terms
- Bacterial Proteins, Catalysis, Fusidic Acid, Models, Molecular, Protein Conformation, Protein Synthesis Inhibitors, Ribosomes, RNA, Bacterial, RNA, Messenger, RNA, Transfer, Protein Biosynthesis, Thermus thermophilus, Protein Structure, Tertiary, Crystallography, X-Ray, Peptide Elongation Factor G
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