Mechanism of membrane-tethered mitochondrial protein synthesis

Science. 2021 Feb 19;371(6531):846-849. doi: 10.1126/science.abe0763.

Abstract

Mitochondrial ribosomes (mitoribosomes) are tethered to the mitochondrial inner membrane to facilitate the cotranslational membrane insertion of the synthesized proteins. We report cryo-electron microscopy structures of human mitoribosomes with nascent polypeptide, bound to the insertase oxidase assembly 1-like (OXA1L) through three distinct contact sites. OXA1L binding is correlated with a series of conformational changes in the mitoribosomal large subunit that catalyze the delivery of newly synthesized polypeptides. The mechanism relies on the folding of mL45 inside the exit tunnel, forming two specific constriction sites that would limit helix formation of the nascent chain. A gap is formed between the exit and the membrane, making the newly synthesized proteins accessible. Our data elucidate the basis by which mitoribosomes interact with the OXA1L insertase to couple protein synthesis and membrane delivery.

Publication types

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

MeSH terms

  • Cryoelectron Microscopy
  • Electron Transport Complex IV / chemistry
  • Electron Transport Complex IV / metabolism*
  • Humans
  • Membrane Proteins / biosynthesis*
  • Membrane Proteins / chemistry
  • Mitochondria / metabolism
  • Mitochondrial Membranes / metabolism
  • Mitochondrial Proteins / chemistry
  • Mitochondrial Proteins / metabolism*
  • Mitochondrial Ribosomes / metabolism*
  • Mitochondrial Ribosomes / ultrastructure
  • Models, Molecular
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • Protein Biosynthesis*
  • Protein Conformation
  • Protein Folding
  • Ribosomes / metabolism

Substances

  • Membrane Proteins
  • Mitochondrial Proteins
  • Nuclear Proteins
  • OXA1 protein
  • Electron Transport Complex IV