Translation elongation cycle.

<p>The ribosome has three tRNA binding sites, the A, P, and E site. A ribosome that has just arrived at a new (green) codon of an mRNA (state “0”) has an empty A site, whereas the P site is occupied by a tRNA (here shown as small gray sphere) that is cognate or near-cognate to the preceding codon. Elongation factor EF-Tu (blue spheres), aa-tRNAs (green, orange, and purple small spheres), and GTP molecules (not shown) form ternary complexes. Free cognate, near-cognate and non-cognate ternary complexes bind to the ribosome with rates depending on their respective concentrations (green, orange, and purple arrows from state “0” to states “1”, “6”, and “11”, respectively). Since the initial binding is not codon-specific, all kinds of ternary complexes unbind again from the ribosome with the same dissociation rate. Alternatively, a cognate or near-cognate ternary complex can be recognized by the ribosome (dotted arrows from states “1” and “6” to states “4” and “9”, respectively) before the ternary complex is either completely released (arrows from states “4” and “9” to state “0”), brought back to the initial binding state (dotted arrows from states “4” and “9’ to states “1” and “6”, respectively), or its aa-tRNA is accommodated in the ribosomal A site (arrows from states “4” and ”9” to states “5” and “10”, respectively). Along with aa-tRNA accommodation, EF-Tu leaves the ribosome. The new A-site tRNA is then further processed and shifted to the P site, while the ribosome translocates to the next (purple) codon. The former P-site tRNA is now in the E site. Depending on the assumed pathway of tRNA release, the E-site tRNA either dissociates very rapidly from the ribosome (2-1-2 pathway), or stays until the next aa-tRNA has been accommodated in the ribosomal A site (2-3-2 pathway). The numerals correspond to the ribosomal states of the codon-specific Markov process introduced below.