Crystal structure of the eukaryotic 60S ribosomal subunit in complex with initiation factor 6

Science. 2011 Nov 18;334(6058):941-8. doi: 10.1126/science.1211204. Epub 2011 Nov 3.


Protein synthesis in all organisms is catalyzed by ribosomes. In comparison to their prokaryotic counterparts, eukaryotic ribosomes are considerably larger and are subject to more complex regulation. The large ribosomal subunit (60S) catalyzes peptide bond formation and contains the nascent polypeptide exit tunnel. We present the structure of the 60S ribosomal subunit from Tetrahymena thermophila in complex with eukaryotic initiation factor 6 (eIF6), cocrystallized with the antibiotic cycloheximide (a eukaryotic-specific inhibitor of protein synthesis), at a resolution of 3.5 angstroms. The structure illustrates the complex functional architecture of the eukaryotic 60S subunit, which comprises an intricate network of interactions between eukaryotic-specific ribosomal protein features and RNA expansion segments. It reveals the roles of eukaryotic ribosomal protein elements in the stabilization of the active site and the extent of eukaryotic-specific differences in other functional regions of the subunit. Furthermore, it elucidates the molecular basis of the interaction with eIF6 and provides a structural framework for further studies of ribosome-associated diseases and the role of the 60S subunit in the initiation of protein synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / metabolism
  • Base Sequence
  • Binding Sites
  • Crystallization
  • Crystallography, X-Ray
  • Cycloheximide / metabolism
  • Eukaryotic Initiation Factors / chemistry*
  • Eukaryotic Initiation Factors / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • Peptide Chain Initiation, Translational
  • Protein Conformation
  • Protein Structure, Secondary
  • Protozoan Proteins / chemistry
  • Protozoan Proteins / metabolism
  • RNA, Protozoan / chemistry
  • RNA, Protozoan / metabolism
  • RNA, Ribosomal / chemistry
  • RNA, Ribosomal / metabolism
  • RNA, Ribosomal, 5.8S / chemistry
  • RNA, Ribosomal, 5.8S / metabolism
  • Ribosomal Proteins / chemistry*
  • Ribosomal Proteins / metabolism
  • Ribosome Subunits, Large, Eukaryotic / chemistry*
  • Ribosome Subunits, Large, Eukaryotic / metabolism
  • Ribosome Subunits, Large, Eukaryotic / ultrastructure
  • Tetrahymena thermophila / chemistry*
  • Tetrahymena thermophila / metabolism


  • Anti-Bacterial Agents
  • Eukaryotic Initiation Factors
  • Protozoan Proteins
  • RNA, Protozoan
  • RNA, Ribosomal
  • RNA, Ribosomal, 5.8S
  • RNA, ribosomal, 26S
  • Ribosomal Proteins
  • Cycloheximide

Associated data

  • OMIM/4A1B
  • PDB/4A17
  • PDB/4A18
  • PDB/4A19
  • PDB/4A1A
  • PDB/4A1C
  • PDB/4A1D
  • PDB/4A1E