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Structure paper

TitleStructural basis of GTPase-mediated mitochondrial ribosome biogenesis and recycling.
Journal, issue, pagesNat Commun, Vol. 12, Issue 1, Page 3672, Year 2021
Publish dateJun 16, 2021
AuthorsHauke S Hillen / Elena Lavdovskaia / Franziska Nadler / Elisa Hanitsch / Andreas Linden / Katherine E Bohnsack / Henning Urlaub / Ricarda Richter-Dennerlein /
PubMed AbstractRibosome biogenesis requires auxiliary factors to promote folding and assembly of ribosomal proteins and RNA. Particularly, maturation of the peptidyl transferase center (PTC) is mediated by ...Ribosome biogenesis requires auxiliary factors to promote folding and assembly of ribosomal proteins and RNA. Particularly, maturation of the peptidyl transferase center (PTC) is mediated by conserved GTPases, but the molecular basis is poorly understood. Here, we define the mechanism of GTPase-driven maturation of the human mitochondrial large ribosomal subunit (mtLSU) using endogenous complex purification, in vitro reconstitution and cryo-EM. Structures of transient native mtLSU assembly intermediates that accumulate in GTPBP6-deficient cells reveal how the biogenesis factors GTPBP5, MTERF4 and NSUN4 facilitate PTC folding. Addition of recombinant GTPBP6 reconstitutes late mtLSU biogenesis in vitro and shows that GTPBP6 triggers a molecular switch and progression to a near-mature PTC state. Additionally, cryo-EM analysis of GTPBP6-treated mature mitochondrial ribosomes reveals the structural basis for the dual-role of GTPBP6 in ribosome biogenesis and recycling. Together, these results provide a framework for understanding step-wise PTC folding as a critical conserved quality control checkpoint.
External linksNat Commun / PubMed:34135319 / PubMed Central
MethodsEM (single particle)
Resolution2.2 - 2.9 Å
Structure data

12865

7of0

EMDB-12865, PDB-7of0:
Structure of a human mitochondrial ribosome large subunit assembly intermediate in complex with MTERF4-NSUN4 (dataset1).
Method: EM (single particle) / Resolution: 2.2 Å

12867

7of2

EMDB-12867, PDB-7of2:
Structure of a human mitochondrial ribosome large subunit assembly intermediate in complex with GTPBP6.
Method: EM (single particle) / Resolution: 2.7 Å

12868

7of3

EMDB-12868, PDB-7of3:
Structure of a human mitochondrial ribosome large subunit assembly intermediate in complex with MTERF4-NSUN4 (dataset2).
Method: EM (single particle) / Resolution: 2.7 Å

12869

7of4

EMDB-12869, PDB-7of4:
Structure of mature human mitochondrial ribosome large subunit in complex with GTPBP6 (PTC conformation 1).
Method: EM (single particle) / Resolution: 2.7 Å

12870

7of5

EMDB-12870, PDB-7of5:
Structure of a human mitochondrial ribosome large subunit assembly intermediate in complex with MTERF4-NSUN4 and GTPBP5 (dataset2).
Method: EM (single particle) / Resolution: 2.9 Å

12871

7of6

EMDB-12871, PDB-7of6:
Structure of mature human mitochondrial ribosome large subunit in complex with GTPBP6 (PTC conformation 2).
Method: EM (single particle) / Resolution: 2.6 Å

12872

7of7

EMDB-12872, PDB-7of7:
Structure of a human mitochondrial ribosome large subunit assembly intermediate in complex with MTERF4-NSUN4 and GTPBP5 (dataset1).
Method: EM (single particle) / Resolution: 2.5 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-MG:
Unknown entry

ChemComp-GTP:
GUANOSINE-5'-TRIPHOSPHATE / GTP, energy-carrying molecule*YM / Guanosine triphosphate

Source
  • homo sapiens (human)
  • human (human)
KeywordsRIBOSOME / Mitochondria / Biogenesis / GTPase / NSUN4 / MTERF4

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