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bioRxiv · 10.1101/2021.06.22.449432

Probing interplays between human XBP1u translational arrest peptide and 80S ribosome

Di Palma, F.·Decherchi, S.·Pardo-Avila, F.·Succi, S.·Levitt, M.·von Heijne, G.·Cavalli, A.
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Abstract

The ribosome stalling mechanism is a crucial biological process; yet its atomistic underpinning is still elusive. In this framework, the XBP1u translational arrest peptide (AP) plays a central role in regulating the Unfolded Protein Response (UPR) in eukaryotic cells. Here, we report multi-microseconds all atom molecular dynamics simulations designed to probe the interactions between the XBP1u AP and the mammalian ribosome exit tunnel, both for the wild type AP and for four mutant variants of different arrest potency. Enhanced sampling simulations allow investigating the AP release process of the different variants shedding light on this complex mechanism. The present outcomes are in qualitative/quantitative agreement with available experimental data. In conclusion, we provide an unprecedented atomistic picture of this biological process and clear-cut insights into the key AP-ribosome interactions.

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Di Palma, F., Decherchi, S., Pardo-Avila, F., Succi, S., Levitt, M., von Heijne, G., Cavalli, A.. 2021-06-22. Probing interplays between human XBP1u translational arrest peptide and 80S ribosome. https://doi.org/10.1101/2021.06.22.449432

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