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A steric gate controls P/E hybrid-state formation of tRNA on the ribosome

Mariana Levi, Kelsey Walak, Ailun Wang, Udayan Mohanty and Paul C. Whitford ()
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Mariana Levi: Northeastern University
Kelsey Walak: Northeastern University
Ailun Wang: Boston College
Udayan Mohanty: Boston College
Paul C. Whitford: Northeastern University

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract The ribosome is a biomolecular machine that undergoes multiple large-scale structural rearrangements during protein elongation. Here, we focus on a conformational rearrangement during translocation, known as P/E hybrid-state formation. Using a model that explicitly represents all non-hydrogen atoms, we simulated more than 120 spontaneous transitions, where the tRNA molecule is displaced between the P and E sites of the large subunit. In addition to predicting a free-energy landscape that is consistent with previous experimental observations, the simulations reveal how a six-residue gate-like region can limit P/E formation, where sub-angstrom structural perturbations lead to an order-of-magnitude change in kinetics. Thus, this precisely defined set of residues represents a novel target that may be used to control functional dynamics in bacterial ribosomes. This theoretical analysis establishes a direct relationship between ribosome structure and large-scale dynamics, and it suggests how next-generation experiments may precisely dissect the energetics of hybrid formation on the ribosome.

Date: 2020
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DOI: 10.1038/s41467-020-19450-0

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