Molecule of the Month
December 2020
SARS-CoV-2 Nsp1 Inhibits Translation by Binding the Ribosomal mRNA Channel

The SARS-CoV-2 non-structural protein 1 (Nsp1) suppresses host innate immune functions. By combining cryoEM and biochemistry, the Mühlemann group (DCB, University of Bern) together with the Ban group (ETH Zürich) showed that SARS-CoV-2 Nsp1 binds to the human 40S subunit in ribosomal complexes by inserting its C-terminal domain into the mRNA channel, where it interferes with mRNA binding. Nsp1 inhibited translation in vitro and in human cells.
Based on structure of the 40S-Nsp1 complex, residues of Nsp1 crucial for mediating translation inhibition were identified and when mutated, Nsp1 lost its capacity to inhibit translation as predicted.

This work was carried out in the group of Prof. Oliver Mühlemann and the group of Prof. Nenad Ban (ETH Zürich).

References:

  • K. Schubert, E. D. Karousis, A. Jomaa, A. Scaiola, B. Echeverria, L.-A. Gurzeler, M. Leibundgut, V. Thiel, O. Mühlemann, N. Ban;
    "SARS-CoV-2 Nsp1 binds the ribosomal mRNA channel to inhibit translation"
    Nat. Struct. Mol. Biol., 2020, 27(10), 959-966; doi:10.1038/s41594-020-0511-8.