| 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. |
