Structures of the human mitochondrial ribosome bound to EF-G1 reveal distinct features of mitochondrial translation elongation

Nat Commun. 2020 Jul 31;11(1):3830. doi: 10.1038/s41467-020-17715-2.


The mammalian mitochondrial ribosome (mitoribosome) and its associated translational factors have evolved to accommodate greater participation of proteins in mitochondrial translation. Here we present the 2.68-3.96 Å cryo-EM structures of the human 55S mitoribosome in complex with the human mitochondrial elongation factor G1 (EF-G1mt) in three distinct conformational states, including an intermediate state and a post-translocational state. These structures reveal the role of several mitochondria-specific (mito-specific) mitoribosomal proteins (MRPs) and a mito-specific segment of EF-G1mt in mitochondrial tRNA (tRNAmt) translocation. In particular, the mito-specific C-terminal extension in EF-G1mt is directly involved in translocation of the acceptor arm of the A-site tRNAmt. In addition to the ratchet-like and independent head-swiveling motions exhibited by the small mitoribosomal subunit, we discover significant conformational changes in MRP mL45 at the nascent polypeptide-exit site within the large mitoribosomal subunit that could be critical for tethering of the elongating mitoribosome onto the inner-mitochondrial membrane.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Cryoelectron Microscopy
  • HEK293 Cells
  • Humans
  • Mitochondria / metabolism*
  • Mitochondria / ultrastructure
  • Mitochondrial Membranes / metabolism
  • Mitochondrial Membranes / ultrastructure
  • Mitochondrial Proteins / chemistry*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Models, Molecular
  • Nucleic Acid Conformation
  • Peptide Chain Elongation, Translational*
  • Peptide Elongation Factor G / chemistry*
  • Peptide Elongation Factor G / genetics
  • Peptide Elongation Factor G / metabolism
  • Protein Binding
  • Protein Conformation, alpha-Helical
  • Protein Conformation, beta-Strand
  • Protein Interaction Domains and Motifs
  • RNA, Mitochondrial / chemistry*
  • RNA, Mitochondrial / genetics
  • RNA, Mitochondrial / metabolism
  • RNA, Transfer / chemistry*
  • RNA, Transfer / genetics
  • RNA, Transfer / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Ribosomal Proteins / chemistry*
  • Ribosomal Proteins / genetics
  • Ribosomal Proteins / metabolism
  • Ribosomes / metabolism*
  • Ribosomes / ultrastructure
  • Sequence Alignment
  • Sequence Homology, Amino Acid


  • GFM1 protein, human
  • Mitochondrial Proteins
  • Peptide Elongation Factor G
  • RNA, Mitochondrial
  • Recombinant Proteins
  • Ribosomal Proteins
  • RNA, Transfer