TY - JOUR TI - Mechanism of completion of peptidyltransferase centre assembly in eukaryotes AU - Kargas, Vasileios AU - Castro-Hartmann, Pablo AU - Escudero-Urquijo, Norberto AU - Dent, Kyle AU - Hilcenko, Christine AU - Sailer, Carolin AU - Zisser, Gertrude AU - Marques-Carvalho, Maria J AU - Pellegrino, Simone AU - WawiĆ³rka, Leszek AU - Freund, Stefan MV AU - Wagstaff, Jane L AU - Andreeva, Antonina AU - Faille, Alexandre AU - Chen, Edwin AU - Stengel, Florian AU - Bergler, Helmut AU - Warren, Alan John A2 - Kuriyan, John A2 - Sonenberg, Nahum A2 - Klinge, Sebastian A2 - Amunts, Alexey VL - 8 PY - 2019 DA - 2019/05/22 SP - e44904 C1 - eLife 2019;8:e44904 DO - 10.7554/eLife.44904 UR - https://doi.org/10.7554/eLife.44904 AB - During their final maturation in the cytoplasm, pre-60S ribosomal particles are converted to translation-competent large ribosomal subunits. Here, we present the mechanism of peptidyltransferase centre (PTC) completion that explains how integration of the last ribosomal proteins is coupled to release of the nuclear export adaptor Nmd3. Single-particle cryo-EM reveals that eL40 recruitment stabilises helix 89 to form the uL16 binding site. The loading of uL16 unhooks helix 38 from Nmd3 to adopt its mature conformation. In turn, partial retraction of the L1 stalk is coupled to a conformational switch in Nmd3 that allows the uL16 P-site loop to fully accommodate into the PTC where it competes with Nmd3 for an overlapping binding site (base A2971). Our data reveal how the central functional site of the ribosome is sculpted and suggest how the formation of translation-competent 60S subunits is disrupted in leukaemia-associated ribosomopathies. KW - ribosome KW - cryo-EM KW - Shwachman-Diamond syndrome KW - ribosomopathy KW - leukaemia KW - SBDS JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -