Poster abstracts

Poster number 148 submitted by Brenna Saladin

Structural basis of ribosomal hibernation across eukaryotes

Brenna Saladin (Department of Biological Chemistry, University of Michigan), Wenzhao Dong (Department of Biological Chemistry, University of Michigan), Fengrong Wang (Department of Biological Chemistry, University of Michigan), Vernon Carruthers (Department of Microbiology and Immunology, University of Michigan), Jailson Brito Querido (Department of Biological Chemistry, University of Michigan)

Abstract:
The ribosome is an essential piece of cellular machinery responsible for translating messenger RNA (mRNA) to produce proteins. Regulating translation is key for cell survival in response to environmental changes. One point of regulation can be ribosomal hibernation, where the 80S ribosome is held within an inactive state, often with the help of other ribosome-associated protein factors. Ribosomal hibernation has been an important focus of study in bacteria; wherein translational regulation can be enacted during stationary phase as well as other stress conditions. However, ribosomal hibernation within eukaryotes is less understood. Here, we have used cryo-EM to determine a high-resolution structure of hibernating ribosomal states in two different eukaryotic organisms: Homo sapiens and the parasite Toxoplasma gondii. Our high-resolution cryo-EM map enabled us to identify potential factors contributing to ribosomal hibernation: eEF2, tRNA, Ebp1, and Serbp1. Ebp1 is present at the peptide exit tunnel of the 80S ribosome only within the human ribosome. However, both tRNA and eEF2 are bound to these inactive ribosomes within both Toxoplasma gondii and humans, indicating a potential conserved of hibernation factor across eukaryotic species. Our data provide new insights into ribosome hibernation, revealing conserved features shared between pathogenic eukaryotes and their mammalian hosts.

References:
Prossliner, T., Winther, K. S., Sørensen, M. A. & Gerdes, K. Ribosome Hibernation. Annu. Rev. Genet. 52, 321–348 (2018).
Wells, J. N. et al. Structure and function of yeast Lso2 and human CCDC124 bound to hibernating ribosomes. PLOS Biol. 18, e3000780 (2020).

Keywords: ribosome hibernation, eEF2, Ebp1