ABSTRACT
Changes in ribosome conformation during protein synthesis are substantial, the most pronounced ones occurring during mRNA-tRNA translocation along the aminoacyl, peptidyl, and exit tRNA binding sites of the ribosome, and shown in studies by cryogenic electron microscopy (cryo-EM), X-ray crystallography, and smFRET. Translocation can be broadly divided into two phases: during the first phase, the tRNAs move with respect to the large subunit, and in the second, the mRNA and the tRNAs affixed to it move with respect to the small subunit. We interpret the states with intermediate intersubunit rotations as intermediates in the transition of the ribosome from the classical to the final, fully rotated configuration. The fact that the conformational changes of the ribosome and classical-hybrid transitions of tRNAs occur spontaneously in a pretranslocational ribosome has confirmed the view of the ribosome as a Brownian machine. The role of ribosomal factors is to modulate the free-energy landscape, promoting structural and kinetic routes underlying functional dynamics of translation.
