title: Steric interactions lead to collective tilting motion in the ribosome during mRNA-tRNA translocation.
abstract: Translocation of mRNA and tRNA through the ribosome is associated with large-scale rearrangements of the head domain in the 30S ribosomal subunit. To elucidate the relationship between 30S head dynamics and mRNA-tRNA displacement, we apply molecular dynamics simulations using an all-atom structure-based model. Here we provide a statistical analysis of 250 spontaneous transitions between the A/P-P/E and P/P-E/E ensembles. Consistent with structural studies, the ribosome samples a chimeric ap/P-pe/E intermediate, where the 30S head is rotated ∼18°. It then transiently populates a previously unreported intermediate ensemble, which is characterized by a ∼10° tilt of the head. To identify the origins of head tilting, we analyse 781 additional simulations in which specific steric features are perturbed. These calculations show that head tilting may be attributed to specific steric interactions between tRNA and the 30S subunit (PE loop and protein S13). Taken together, this study demonstrates how molecular structure can give rise to large-scale collective rearrangements.
authors.affiliation: Department of Physics, Northeastern University, Dana Research Center 111, 360 Huntington Avenue, Boston, Massachusetts 02115, USA.
authors.forename: Kien
authors.initials: K
authors.lastname: Nguyen
authors.affiliation: Department of Physics, Northeastern University, Dana Research Center 111, 360 Huntington Avenue, Boston, Massachusetts 02115, USA.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Whitford
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009038:Motion; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012343:RNA, Transfer / Q000235:genetics / Q000378:metabolism*; D054681:Ribosome Subunits, Large, Bacterial / Q000378:metabolism*; D054680:Ribosome Subunits, Small, Bacterial / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D012343:RNA, Transfer
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