Figure 6 Model of AGA-induced error cluster formation

The efficacy of an AGA in inducing proteotoxic error clusters depends on its ability to bind and induce the 1^st error, its residence time on the ribosome and the inhibitory effect on translocation. Str, which does not affect translocation, and its derivative DHS, induce frequent single errors and remain bound to the ribosome for many elongation cycles, resulting in formation of long error clusters. AGAs that have a moderate inhibitory effect on translocation induce short clusters, because they tend to dissociate after only a few slow translation rounds. Neamine has a high misreading potential, but dissociates rapidly from the ribosome, resulting in low levels of presumably stochastic error clusters which are thus not distance dependence. Viomycin stops translocation which terminates translation by ribosomes that have the antibiotic bound and hence prevents formation of the error clusters.