Models for two tRNAs bound to successive codons on mRNA on the ribosome

We have investigated the structural changes necessary to build a model complex of two molecules of phenylalanine transfer RNA (tRNA(Phe) bound to successive codons in a short segment of a model messenger RNA (mRNA), consisting of U6. We keep the mRNA in an ideal helical conformation, deforming the tRNAs as necessary to eliminate steric overlaps while bringing the two 3' termini together. The resulting model has the two tRNAs oriented relative to one another in a manner that is very similar to a model developed by McDonald and Rein (1) in which the tRNAs maintain their ideal crystallographic conformations and all of the deformations are introduced into the mRNA. Consequently, regardless of how one divides the deformations between the tRNAs and the mRNA it is clear that, on the ribosome, the tRNA in the P site has its "front" side (that side with the variable loop) close to the "back" side of the tRNA in the A site (that side with the D loop). The space between the two molecules must be left free on the ribosome, in order to facilitate the transition from the A site to the P site. A detailed pathway is also proposed for changing the anticodon loop structure from that of the A site to that of the P site. The anticodon loop is always kept in a 3'-stacked conformation, since we find that the shift between the 3'-stacked and 5'-stacked structures proposed by Woese (2) is not feasible.