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Elongation Factor Tu Switch I Element is a Gate for Aminoacyl-tRNA Selection
Dylan Girodat1, Scott C Blanchard2, Hans-Joachim Wieden3
1Theoretical Biology and Biophysics Group, Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM, 87545, USA.
Journal of Molecular Biology
|February 17, 2020
Summary
Elongation factor EF-Tu's switch I region plays a key role in ensuring translational accuracy. This structural element guides aminoacyl-tRNA selection by interacting with the tRNA acceptor stem, enhancing protein synthesis fidelity.
Area of Science:
- Molecular Biology
- Structural Biology
- Biochemistry
Background:
- Accurate aminoacyl-tRNA (aa-tRNA) selection at the ribosomal A site is crucial for translational fidelity.
- Elongation factor EF-Tu facilitates aa-tRNA delivery and selection, but its proofreading mechanism requires further elucidation.
Purpose of the Study:
- To investigate the structural mechanism by which EF-Tu contributes to aa-tRNA selection and translational fidelity.
- To elucidate the role of EF-Tu's switch I region in the aa-tRNA accommodation process.
Main Methods:
- Structure-based and explicit solvent molecular dynamics simulations.
- Analysis of EF-Tu conformational changes from GTP to GDP states during aa-tRNA accommodation.
- Utilizing cryo-electron microscopy reconstructions.
Main Results:
- EF-Tu's switch I region undergoes a rapid conformational change from an α-helix to a β-hairpin during aa-tRNA accommodation.
- Switch I interacts with the aa-tRNA acceptor stem, sterically gating its movement and contributing to selection.
- Pharmacological inhibition disrupts switch I-tRNA interaction, confirming specificity for cognate aa-tRNA substrates.
Conclusions:
- Switch I of EF-Tu is a critical determinant in the aa-tRNA selection process.
- The observed interactions of switch I with the aa-tRNA acceptor stem provide a mechanism for enhancing translational fidelity.
- This finding offers insights into the structural basis of protein synthesis accuracy.
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