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Nascent chain dynamics and ribosome interactions within folded ribosome–nascent chain complexes observed by NMR spectroscopy

The folding of many proteins can begin during biosynthesis on the ribosome and can be modulated by the ribosome itself. Such perturbations are generally believed to be mediated through interactions between the nascent chain and the ribosome surface, but despite recent progress in characterising inte...

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Autores principales: Burridge, Charles, Waudby, Christopher A., Włodarski, Tomasz, Cassaignau, Anaïs M. E., Cabrita, Lisa D., Christodoulou, John
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8513902/
https://www.ncbi.nlm.nih.gov/pubmed/34745542
http://dx.doi.org/10.1039/d1sc04313g
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author Burridge, Charles
Waudby, Christopher A.
Włodarski, Tomasz
Cassaignau, Anaïs M. E.
Cabrita, Lisa D.
Christodoulou, John
author_facet Burridge, Charles
Waudby, Christopher A.
Włodarski, Tomasz
Cassaignau, Anaïs M. E.
Cabrita, Lisa D.
Christodoulou, John
author_sort Burridge, Charles
collection PubMed
description The folding of many proteins can begin during biosynthesis on the ribosome and can be modulated by the ribosome itself. Such perturbations are generally believed to be mediated through interactions between the nascent chain and the ribosome surface, but despite recent progress in characterising interactions of unfolded states with the ribosome, and their impact on the initiation of co-translational folding, a complete quantitative analysis of interactions across both folded and unfolded states of a nascent chain has yet to be realised. Here we apply solution-state NMR spectroscopy to measure transverse proton relaxation rates for methyl groups in folded ribosome–nascent chain complexes of the FLN5 filamin domain. We observe substantial increases in relaxation rates for the nascent chain relative to the isolated domain, which can be related to changes in effective rotational correlation times using measurements of relaxation and cross-correlated relaxation in the isolated domain. Using this approach, we can identify interactions between the nascent chain and the ribosome surface, driven predominantly by electrostatics, and by measuring the change in these interactions as the subsequent FLN6 domain emerges, we may deduce their impact on the free energy landscapes associated with the co-translational folding process.
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spelling pubmed-85139022021-11-04 Nascent chain dynamics and ribosome interactions within folded ribosome–nascent chain complexes observed by NMR spectroscopy Burridge, Charles Waudby, Christopher A. Włodarski, Tomasz Cassaignau, Anaïs M. E. Cabrita, Lisa D. Christodoulou, John Chem Sci Chemistry The folding of many proteins can begin during biosynthesis on the ribosome and can be modulated by the ribosome itself. Such perturbations are generally believed to be mediated through interactions between the nascent chain and the ribosome surface, but despite recent progress in characterising interactions of unfolded states with the ribosome, and their impact on the initiation of co-translational folding, a complete quantitative analysis of interactions across both folded and unfolded states of a nascent chain has yet to be realised. Here we apply solution-state NMR spectroscopy to measure transverse proton relaxation rates for methyl groups in folded ribosome–nascent chain complexes of the FLN5 filamin domain. We observe substantial increases in relaxation rates for the nascent chain relative to the isolated domain, which can be related to changes in effective rotational correlation times using measurements of relaxation and cross-correlated relaxation in the isolated domain. Using this approach, we can identify interactions between the nascent chain and the ribosome surface, driven predominantly by electrostatics, and by measuring the change in these interactions as the subsequent FLN6 domain emerges, we may deduce their impact on the free energy landscapes associated with the co-translational folding process. The Royal Society of Chemistry 2021-09-09 /pmc/articles/PMC8513902/ /pubmed/34745542 http://dx.doi.org/10.1039/d1sc04313g Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/
spellingShingle Chemistry
Burridge, Charles
Waudby, Christopher A.
Włodarski, Tomasz
Cassaignau, Anaïs M. E.
Cabrita, Lisa D.
Christodoulou, John
Nascent chain dynamics and ribosome interactions within folded ribosome–nascent chain complexes observed by NMR spectroscopy
title Nascent chain dynamics and ribosome interactions within folded ribosome–nascent chain complexes observed by NMR spectroscopy
title_full Nascent chain dynamics and ribosome interactions within folded ribosome–nascent chain complexes observed by NMR spectroscopy
title_fullStr Nascent chain dynamics and ribosome interactions within folded ribosome–nascent chain complexes observed by NMR spectroscopy
title_full_unstemmed Nascent chain dynamics and ribosome interactions within folded ribosome–nascent chain complexes observed by NMR spectroscopy
title_short Nascent chain dynamics and ribosome interactions within folded ribosome–nascent chain complexes observed by NMR spectroscopy
title_sort nascent chain dynamics and ribosome interactions within folded ribosome–nascent chain complexes observed by nmr spectroscopy
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8513902/
https://www.ncbi.nlm.nih.gov/pubmed/34745542
http://dx.doi.org/10.1039/d1sc04313g
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