From machine to man: the physics of protein synthesis

 

Brooks and his colleague, postdoctoral associate Florence Tama, are exploring how the functioning of Nature's machines can be captured with simple mechanical models from physics. The ribosome, which is responsible for the synthesis of proteins, undergoes a range of structural changes during protein synthesis. Two key motions that have been characterized via the lower-resolution structural methods of cyo-electron microscopy involve the ratchet-like displacement of the major ribosomal domains (30S and 50S subunits) with respect to each opther, which occurs during the translocation of tRNA from the A and P binding sites to the P and E sites (left panel, tRNA shown as red and green wire models), and large-scale displacement of the protein L1, which has been suggested to facilitate the dissociation of amino acid exhausted tRNA from the E site (right panel). Using elasto-mechanical models based on the crystallographic structure of the 70S ribosome, Tama and Brooks have shown that these functionally critical motions arise as natural displacements of "elastic bodies" with the shape of the ribosome. Emerging from their calculations are atomic-level pathways for these steps in translocation. In particular, they show that the ratchet-like rotation of the 50S subunit relative to 30S leads to initial displacement of the tRNA molecules in A and P sites toward the P and E sites (depicted in left panel). Also prevalent as a "normal mode" of displacement of the complex is the "reaching" of the L1 protein "arm" to possibly facilitate the removal of spent tRNA in the E site (shown in the right panel: the pivot point for L1 motion is denoted by the red dot and three positions of the protein relative to the 50S subunit are denoted as I-III, the tRNA is shown in red, green and pink wire models). The hypothesis that evolves from these investigations, as well as others exploring biology's machines, is that Nature builds robustness into the functioning of these machines by assembling particular shapes, and that it is this shape which dominates the character of the most facile motions used in achieving function in such assemblies.