Regulation of the Mammalian Elongation Cycle by Subunit Rolling: A Eukaryotic-Specific Ribosome Rearrangement

The extent to which bacterial ribosomes and the significantly larger eukaryotic ribosomes share the same mechanisms of ribosomal elongation is unknown. Here, we present subnanometer resolution cryoelectron microscopy maps of the mammalian 80S ribosome in the posttranslocational state and in complex with the eukaryotic eEF1A⋅Val-tRNA⋅GMPPNP ternary complex, revealing significant differences in the elongation mechanism between bacteria and mammals. Surprisingly, and in contrast to bacterial ribosomes, a rotation of the small subunit around its long axis and orthogonal to the well-known intersubunit rotation distinguishes the posttranslocational state from the classical pretranslocational state ribosome. We term this motion “subunit rolling.” Correspondingly, a mammalian decoding complex visualized in substates before and after codon recognition reveals structural distinctions from the bacterial system. These findings suggest how codon recognition leads to GTPase activation in the mammalian system and demonstrate that in mammalia subunit rolling occurs during tRNA selection. [Display omitted] •The structure of mammalian POST translocation complex at subnanometer resolution•Structures of two substates of the mammalian decoding complex•Subunit rolling: a eukaryotic-specific conformational change in the ribosome•A seesaw-like model for GTPase activation during mammalian tRNA selection The analyses of the mammalian 80S ribosome in various steps of translation elongation by cryoelectron microscopy reveal surprising structural distinctions from the bacterial system, including a eukaryotic-specific conformational change called subunit rolling.