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The ribosome stabilizes partially folded intermediates of a nascent multi-domain protein



Chan, Sammy HS;

Włodarski, Tomasz;

Streit, Julian O;

Cassaignau, Anaïs ME;

Woodburn, Lauren F;

Ahn, Minkoo;

Freiherr von Sass, Georg Johannes;

Christodoulou, John; + view all

Chan, Sammy HS;

Włodarski, Tomasz;

Streit, Julian O;

Cassaignau, Anaïs ME;

Woodburn, Lauren F;

Ahn, Minkoo;

Freiherr von Sass, Georg Johannes;

Waudby, Christopher A;

Budisa, Nediljko;

Cabrita, Lisa D;

Christodoulou, John;

– view fewer

(2022)

The ribosome stabilizes partially folded intermediates of a nascent multi-domain protein.

Nature Chemistry


10.1038/s41557-022-01004-0.

Abstract

Co-translational folding is crucial to ensure the production of biologically active proteins. The ribosome can alter the folding pathways of nascent polypeptide chains, yet a structural understanding remains largely inaccessible experimentally. We have developed site-specific labelling of nascent chains to detect and measure, using 19F nuclear magnetic resonance (NMR) spectroscopy, multiple states accessed by an immunoglobulin-like domain within a tandem repeat protein during biosynthesis. By examining ribosomes arrested at different stages during translation of this common structural motif, we observe highly broadened NMR resonances attributable to two previously unidentified intermediates, which are stably populated across a wide folding transition. Using molecular dynamics simulations and corroborated by cryo-electron microscopy, we obtain models of these partially folded states, enabling experimental verification of a ribosome-binding site that contributes to their high stabilities. We thus demonstrate a mechanism by which the ribosome could thermodynamically regulate folding and other co-translational processes.

Type: Article

Title: The ribosome stabilizes partially folded intermediates of a nascent multi-domain protein
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41557-022-01004-0
Publisher version: https://doi.org/10.1038/s41557-022-01004-0
Language: English
Additional information: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
UCL classification: 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 > Structural and Molecular Biology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
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 > UCL School of Pharmacy
URI: https://discovery.ucl.ac.uk/id/eprint/10153390
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