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Common sequence motifs of nascent chains engage the ribosome surface and trigger factor

Deckert, A; Cassaignau, AME; Wang, X; Włodarski, T; Chan, SHS; Waudby, CA; Kirkpatrick, JP; ... Christodoulou, J; + view all (2021) Common sequence motifs of nascent chains engage the ribosome surface and trigger factor. Proceedings of the National Academy of Sciences , 118 (52) , Article e2103015118. 10.1073/pnas.2103015118. Green open access

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Abstract

In the cell, the conformations of nascent polypeptide chains during translation are modulated by both the ribosome and its associated molecular chaperone, trigger factor. The specific interactions that underlie these modulations, however, are still not known in detail. Here, we combine protein engineering, in-cell and in vitro NMR spectroscopy, and molecular dynamics simulations to explore how proteins interact with the ribosome during their biosynthesis before folding occurs. Our observations of α-synuclein nascent chains in living Escherichia coli cells reveal that ribosome surface interactions dictate the dynamics of emerging disordered polypeptides in the crowded cytosol. We show that specific basic and aromatic motifs drive such interactions and directly compete with trigger factor binding while biasing the direction of the nascent chain during its exit out of the tunnel. These results reveal a structural basis for the functional role of the ribosome as a scaffold with holdase characteristics and explain how handover of the nascent chain to specific auxiliary proteins occurs among a host of other factors in the cytosol.

Type: Article
Title: Common sequence motifs of nascent chains engage the ribosome surface and trigger factor
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1073/pnas.2103015118
Publisher version: https://doi.org/10.1073/pnas.2103015118
Language: English
Additional information: Copyright © 2021 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
Keywords: NMR spectroscopy, alpha synuclein, cotranslational folding, in-cell NMR, structural biology
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10140921
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