MetAP-like Ebp1 occupies the human ribosomal tunnel exit and recruits flexible rRNA expansion segments

Human Ebp1 is a member of the proliferation-associated 2G4 (PA2G4) family and plays an important role in cancer regulation. Ebp1 shares the methionine aminopeptidase (MetAP) fold and binds to mature 80S ribosomes for translational control. Here, we present a cryo-EM single particle analysis reconstruction of Ebp1 bound to non-translating human 80S ribosomes at a resolution range from 3.3 to ~8 Å. Ebp1 blocks the tunnel exit with major interactions to the general uL23/uL29 docking site for nascent chain-associated factors complemented by eukaryote-specific eL19 and rRNA helix H59. H59 is defined as dynamic adaptor undergoing significant remodeling upon Ebp1 binding. Ebp1 recruits rRNA expansion segment ES27L to the tunnel exit via specific interactions with rRNA consensus sequences. The Ebp1-ribosome complex serves as a template for MetAP binding and provides insights into the structural principles for spatial coordination of co-translational events and molecular triage at the ribosomal tunnel exit.


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The following cryo-EM densities for the Ebp1-ribosome complex have been deposited in the EMDataBank: Ebp1-60S segment at full-spatial resolution from 2-body multibody refinement (EMD-10610); Ebp1-ES27L segment from 3-body multibody refinement (EMD-10609); Ebp1-60S segment from 2-body multibody refinement after sorting for ES27L conformation (EMD-10608). The atomic coordinates for Ebp1 and interacting ribosomal components have been deposited in the RCSB with accession ID 6SXO. For visualization of the model in context of the entire human 80S ribosome, we recommend to superpose our atomic coordinates to the structure of the human ribosome solved at 2.9 Å resolution (PDB-ID 6EK0), which is virtually identical except for the Ebp1-interacting region. Other data are available from the corresponding authors upon reasonable request.