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

摘要

Human Ebp1 is a member of the proliferation-associated 2G4 (PA2G4) family and plays animportant 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-EMsingle particle analysis reconstruction of Ebp1 bound to non-translating human 80S ribosomesat a resolution range from 3.3 to ~8 ?. Ebp1 blocks the tunnel exit with major interactionsto the general uL23/uL29 docking site for nascent chain-associated factorscomplemented by eukaryote-specific eL19 and rRNA helix H59. H59 is defined as dynamicadaptor undergoing significant remodeling upon Ebp1 binding. Ebp1 recruits rRNA expansionsegment 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 insightsinto the structural principles for spatial coordination of co-translational events and moleculartriage at the ribosomal tunnel exit.