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Structure paper

TitleMechanism of completion of peptidyltransferase centre assembly in eukaryotes.
Journal, issue, pagesElife, Vol. 8, Year 2019
Publish dateMay 22, 2019
AuthorsVasileios Kargas / Pablo Castro-Hartmann / Norberto Escudero-Urquijo / Kyle Dent / Christine Hilcenko / Carolin Sailer / Gertrude Zisser / Maria J Marques-Carvalho / Simone Pellegrino / Leszek Wawiórka / Stefan Mv Freund / Jane L Wagstaff / Antonina Andreeva / Alexandre Faille / Edwin Chen / Florian Stengel / Helmut Bergler / Alan John Warren /
PubMed AbstractDuring 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 ...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.
External linksElife / PubMed:31115337 / PubMed Central
MethodsEM (single particle)
Resolution3.1 - 3.9 Å
Structure data

EMDB-10039:
Cryo-EM structures of Lsg1-TAP pre-60S ribosomal particles (State V - subclass 1)
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-10066:
Cryo-EM structure of Lsg1-TAP pre-60S ribosomal particles (State I - subclass 1)
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-10067:
Cryo-EM structure of Lsg1-TAP ribosomal subunit (State I - subclass 2)
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-10068, PDB-6rzz:
Cryo-EM structures of Lsg1-TAP pre-60S ribosomal particles
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-10070:
Cryo-EM structure of Lsg1-TAP pre-60S ribosomal particles (State II - subclass 1)
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-10071, PDB-6s05:
Cryo-EM structures of Lsg1-TAP pre-60S ribosomal particles
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-4560, PDB-6qik:
Cryo-EM structures of Lsg1-TAP pre-60S ribosomal particles
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-4630, PDB-6qt0:
Cryo-EM structures of Lsg1-TAP pre-60S ribosomal particles
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-4636, PDB-6qtz:
Cryo-EM structures of Lsg1-TAP pre-60S ribosomal particles
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-4884, PDB-6ri5:
Cryo-EM structures of Lsg1-TAP pre-60S ribosomal particles
Method: EM (single particle) / Resolution: 3.3 Å

Chemicals

ChemComp-ZN:
Unknown entry

Source
  • saccharomyces cerevisiae (brewer's yeast)
  • Baker's yeast (brewer's yeast)
KeywordsRIBOSOME / 60S subunit / eIF6 / Nmd3 / Lsg1

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