Structures of translationally inactive mammalian ribosomes

Elife. 2018 Oct 24;7:e40486. doi: 10.7554/eLife.40486.


The cellular levels and activities of ribosomes directly regulate gene expression during numerous physiological processes. The mechanisms that globally repress translation are incompletely understood. Here, we use electron cryomicroscopy to analyze inactive ribosomes isolated from mammalian reticulocytes, the penultimate stage of red blood cell differentiation. We identify two types of ribosomes that are translationally repressed by protein interactions. The first comprises ribosomes sequestered with elongation factor 2 (eEF2) by SERPINE mRNA binding protein 1 (SERBP1) occupying the ribosomal mRNA entrance channel. The second type are translationally repressed by a novel ribosome-binding protein, interferon-related developmental regulator 2 (IFRD2), which spans the P and E sites and inserts a C-terminal helix into the mRNA exit channel to preclude translation. IFRD2 binds ribosomes with a tRNA occupying a noncanonical binding site, the 'Z site', on the ribosome. These structures provide functional insights into how ribosomal interactions may suppress translation to regulate gene expression.

Keywords: electron cryomicroscopy; in vitro reconstitution; molecular biophysics; none; ribosome; structural biology.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • HEK293 Cells
  • Humans
  • Mammals / metabolism*
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism
  • Models, Molecular
  • Molecular Conformation
  • Peptide Elongation Factor 2 / metabolism
  • Protein Binding
  • Protein Biosynthesis*
  • RNA, Transfer / metabolism
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / metabolism
  • Rabbits
  • Reticulocytes / metabolism
  • Ribosomes / metabolism*
  • Ribosomes / ultrastructure*


  • Membrane Proteins
  • Peptide Elongation Factor 2
  • RNA-Binding Proteins
  • RNA, Transfer