Mechanism of completion of peptidyltransferase centre assembly in eukaryotes
Mechanism of completion of peptidyltransferase centre assembly in eukaryotes
Date
2019
Authors
Kargas, Vasileios
Castro-Hartmann, Pablo
Escudero-Urquijo, Norberto
Dent, Kyle
Hilcenko, Christine
Zisser, Gertrude
Marques-Carvalho, Maria J
Pellegrino, Simone
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eLife ; 8 (2019). - e44904. - eISSN 2050-084X
Abstract
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.
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KARGAS, Vasileios, Pablo CASTRO-HARTMANN, Norberto ESCUDERO-URQUIJO, Kyle DENT, Christine HILCENKO, Carolin SAILER, Gertrude ZISSER, Maria J MARQUES-CARVALHO, Simone PELLEGRINO, Florian STENGEL, 2019. Mechanism of completion of peptidyltransferase centre assembly in eukaryotes. In: eLife. 8, e44904. eISSN 2050-084X. Available under: doi: 10.7554/eLife.44904BibTex
@article{Kargas2019Mecha-47754, year={2019}, doi={10.7554/eLife.44904}, title={Mechanism of completion of peptidyltransferase centre assembly in eukaryotes}, volume={8}, journal={eLife}, author={Kargas, Vasileios and Castro-Hartmann, Pablo and Escudero-Urquijo, Norberto and Dent, Kyle and Hilcenko, Christine and Sailer, Carolin and Zisser, Gertrude and Marques-Carvalho, Maria J and Pellegrino, Simone and Stengel, Florian}, note={Article Number: e44904} }
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