Structural basis of GTPase-mediated mitochondrial ribosome biogenesis and recycling

Nat Commun. 2021 Jun 16;12(1):3672. doi: 10.1038/s41467-021-23702-y.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cryoelectron Microscopy
  • GTP-Binding Proteins / chemistry*
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism
  • Humans
  • Methyltransferases / chemistry
  • Methyltransferases / metabolism
  • Mitochondrial Ribosomes / chemistry*
  • Mitochondrial Ribosomes / metabolism
  • Models, Molecular
  • Monomeric GTP-Binding Proteins / chemistry*
  • Monomeric GTP-Binding Proteins / metabolism
  • Multiprotein Complexes
  • Organelle Biogenesis
  • Peptidyl Transferases / chemistry
  • Peptidyl Transferases / metabolism
  • Protein Folding
  • RNA, Ribosomal / chemistry
  • RNA, Ribosomal / metabolism
  • Ribosome Subunits, Large / chemistry
  • Ribosome Subunits, Large / metabolism
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism


  • GTPBP6 protein, human
  • MTERF4 protein, human
  • Multiprotein Complexes
  • RNA, Ribosomal
  • Transcription Factors
  • Methyltransferases
  • NSUN4 protein, human
  • Peptidyl Transferases
  • GTP-Binding Proteins
  • MTG2 protein, human
  • Monomeric GTP-Binding Proteins