Molecular dynamics of EF‐G during translocation
Open accessAbstract
Elongation factor G (EF‐G) plays a crucial role in two stages of mRNA‐(tRNA) 2 translocation. First, EF‐G•GTP enters the pre‐translocational ribosome in its intersubunit‐rotated state, with tRNAs in their hybrid (P/E and A/P) positions. Second, a conformational change in EF‐G's Domain IV induced by GTP hydrolysis disengages the mRNA‐anticodon stem‐loops of the tRNAs from the decoding center to advance relative to the small subunit when the ribosome undergoes a backward inter‐subunit rotation. These events take place as EF‐G undergoes a series of large conformational changes as visualized by cryo‐EM and X‐ray studies. The number and variety of these structures leave open many questions on how these different configurations form during the dynamic translocation process. To understand the molecular mechanism of translocation, we examined the molecular motions of EF‐G in solution by means of molecular dynamics simulations. Our results show: (1) rotations of the super‐domain formed by Domains III–V with respect to the super‐domain formed by I–II, and rotations of Domain IV with respect to Domain III; (2) flexible conformations of both 503‐ and 575‐loops; (3) large conformational variability in the bound form caused by the interaction between Domain V and the GTPase‐associated center; (4) after GTP hydrolysis, the Switch I region seems to be instrumental for effecting the conformational change at the end of Domain IV implicated in the disengagement of the codon‐anticodon helix from the decoding center. Proteins 2011; © 2011 Wiley‐Liss, Inc.
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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 [24]
GTP hydrolysis induces substantial conformational changes in the ribosome.
“It is known that GTP hydrolysis induces substantial conformational changes in the ribosome.”
From Mechanism of tetracycline resistance by ribosomal protection protein Tet(O) (2013) · cites this paper as [24]
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Mechanism of tetracycline resistance by ribosomal protection protein Tet(O)
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., et al. (2013) · Nature Communications · doi:10.1038/ncomms2470 · Cited by 147 · see citing works
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- Authors
- Li, W., Trabuco, L. G., Schulten, K., & Frank, J.
- Affiliations
- Columbia University (US)
- University of Illinois Urbana-Champaign (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Frank, Joachim
- Venue
- Proteins: Structure, Function, and Bioinformatics
- Publisher
- Wiley
- Published
- 2011-03
- Volume
- 79
- Issue
- 5
- Pages
- 1478-1486
- ISSN
- 0887-3585 (ISSN-L)
- 1097-0134
- PMC
- PMC3132869
- OpenAlex
- W2001999088
- Cited by
- 38
- References
- 34
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2022: 1 · 2020: 3 · 2018: 1 · 2017: 2 · 2016: 5 · 2015: 2 · 2014: 7 · 2013: 4 · 2012: 8
- FWCI
- 2.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proteins Structure Function and Bioinformatics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Joachim Frank (HHMI, NIH R01 GM 55440)
- Klaus Schulten (NIH P41-RR005969, NSF PHY0822613)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- Keywords
- elongation factor G, mRNA translocation, ribosome, GTP hydrolysis, conformational change, domain IV, switch I, decoding center, molecular dynamics simulation
- MeSH terms
- Bacterial Proteins, Guanosine Triphosphate, Protein Conformation, Ribosomes, RNA, Transfer, Thermus thermophilus, Protein Structure, Tertiary, Peptide Elongation Factor G, Protein Subunits, Molecular Dynamics Simulation
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