Open AccessProbing Interplays between Human XBP1u Translational Arrest Peptide and 80S Ribosome
Author(s) -
Francesco Di Palma,
Sergio Decherchi,
Fátima PardoÁvila,
Sauro Succi,
Michael Levitt,
Gunnar von Heijne,
Andrea Cavalli
Publication year - 2021
Publication title -
journal of chemical theory and computation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.001
H-Index - 185
eISSN - 1549-9626
pISSN - 1549-9618
DOI - 10.1021/acs.jctc.1c00796
Subject(s) - ribosome , computational biology , translation (biology) , mechanism (biology) , microbiology and biotechnology , biophysics , chemistry , biology , physics , rna , messenger rna , biochemistry , gene , quantum mechanics
The ribosome stalling mechanism is a crucial biological process, yet its atomistic underpinning is still elusive. In this framework, the human XBP1u translational arrest peptide (AP) plays a central role in regulating the unfolded protein response (UPR) in eukaryotic cells. Here, we report multimicrosecond 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 potencies. 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.