Biopolym. Cell. 2023; 39(4):265-276.
Structure and Function of Biopolymers
Structural characterization of cephaeline binding to the eukaryotic ribosome using Cryo-Electron Microscopy
1Kolosova O., 1Zgadzay Y., 2Stetsenko A., 2Atamas A., 3Wu C., 3Sachs M. S., 1Jenner L., 2Guskov A., 1Yusupov M.
  1. Department of Integrated Structural Biology, Institute of Genetics and Molecular and Cellular Biology
    University of Strasbourg, Illkirch, 67400, France
  2. Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen
    Groningen, 9747 AG, the Netherlands
  3. Department of Biology, Texas A&M University
    College Station, TX, USA


Aim. In our work, we aimed to elucidate the binding mechanism of another alkaloid, cephaeline, to the eukaryotic ribosome. Methods. We used cryogenic electron microscopy and cell-free assays to reveal its mechanism of action. Results. Our results indicate that cephaeline binds to the E-tRNA binding site on the small subunit of the eukaryotic ribosome. Similar to emetine, cephaeline forms a stacking interaction with G841 of 18S rRNA and L132 of the protein uS11. We propose the hypothesis of cephaeline specificity to eukaryotes by comparing the interaction pattern of cephaeline with other inhibitors binding to the E-site of the mRNA tunnel. Conclusions. The high-resolution structure of ribosome-bound cephaeline (2.45 Å) allowed us to precisely determine the inhibitor’s position in the binding site, which holds potential for the development of the next generation of drugs targeting the mRNA tunnel of the ribosome.
Keywords: ribosome, cephaeline, anti-protozoan, cryo-EM


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