Figure 2.
The kinetic framework for programmed –1 ribosomal frameshifting. Top: the procedure from PA to E0P0 represents translocation, which involves r1, r–1 (reversible EF-G binding), rTL0 (GTP hydrolysis, unlocking conformation change, tRNA movement and Pi release), and r45 (re-locking conformation change and EF-G dissociation). The E0P0 complex then undergoes aa-tRNA selection: from E0P0 to P0A0. The selection of aa-tRNA involves: k1, k–1 (reversible EF-Tu binding), k2, k–2 (reversible codon recognition), k345 (GTPase activation, GTP hydrolysis, EF-Tu conformation change and dissociation), and k6 (aa-tRNA rejection by proofreading), or k7 (aa-tRNA accommodation). The elongation cycle without a –1 PRF event results in synthesis of non-frameshift proteins (NFS). Pathway I in green suggests that –1 PRF occurs during the relocking step in the first translocation, leading to the formation of FSm. Pathway Ia indicates that the E02P02 complex may interact with a zero frame aa-tRNA and eventually produce FSz. Pathways II suggests that –1 PRF occurs during aa-tRNA selection and accommodation, resulting in FSz. Pathway III suggests that –1 PRF occurs during the second translocation step, resulting in FSz production.