Dynamic association of human Ebp1 with the ribosome

RNA. 2021 Apr;27(4):411-419. doi: 10.1261/rna.077602.120. Epub 2021 Jan 21.


Ribosomes are the macromolecular machines at the heart of protein synthesis; however, their function can be modulated by a variety of additional protein factors that directly interact with them. Here, we report the cryo-EM structure of human Ebp1 (p48 isoform) bound to the human 80S ribosome at 3.3 Å resolution. Ebp1 binds in the vicinity of the peptide exit tunnel on the 80S ribosome, and this binding is enhanced upon puromycin-mediated translational inhibition. The association of Ebp1 with the 80S ribosome centers around its interaction with ribosomal proteins eL19 and uL23 and the 28S rRNA. Further analysis of the Ebp1-ribosome complex suggests that Ebp1 can rotate around its insert domain, which may enable it to assume a wide range of conformations while maintaining its interaction with the ribosome. Structurally, Ebp1 shares homology with the methionine aminopeptidase 2 family of enzymes; therefore, this inherent flexibility may also be conserved.

Keywords: Ebp1; ribosome; single-particle cryo-EM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry*
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Binding Sites
  • Cryoelectron Microscopy
  • Humans
  • Models, Molecular
  • Protein Binding
  • Protein Biosynthesis* / drug effects
  • Protein Conformation, alpha-Helical
  • Protein Conformation, beta-Strand
  • Protein Interaction Domains and Motifs
  • Protein Synthesis Inhibitors / pharmacology
  • Puromycin / pharmacology
  • RNA, Ribosomal / chemistry*
  • RNA, Ribosomal / genetics
  • RNA, Ribosomal / metabolism
  • RNA-Binding Proteins / chemistry*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Ribosomal Proteins / chemistry*
  • Ribosomal Proteins / genetics
  • Ribosomal Proteins / metabolism
  • Ribosomes / chemistry*
  • Ribosomes / genetics
  • Ribosomes / metabolism
  • Thermodynamics


  • Adaptor Proteins, Signal Transducing
  • PA2G4 protein, human
  • Protein Synthesis Inhibitors
  • RNA, Ribosomal
  • RNA-Binding Proteins
  • Ribosomal Proteins
  • Puromycin