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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Veröffentlicht in:Chemical science (Cambridge) 2021-10, Vol.12 (39), p.1312-13126
Hauptverfasser: Burridge, Charles, Waudby, Christopher A, W odarski, Tomasz, Cassaignau, Anaïs M. E, Cabrita, Lisa D, Christodoulou, John
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container_issue 39
container_start_page 1312
container_title Chemical science (Cambridge)
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creator Burridge, Charles
Waudby, Christopher A
W odarski, Tomasz
Cassaignau, Anaïs M. E
Cabrita, Lisa D
Christodoulou, John
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. NMR measurements of methyl relaxation in translationally-arrested ribosome-nascent chain complexes probe the dynamics of folded nascent polypeptides emerging during biosynthesis and quantify their interaction with the ribosome surface.
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subjects Biosynthesis
Chain dynamics
Chemistry
Domains
Electrostatics
Folding
Free energy
NMR spectroscopy
Perturbation
Spectrum analysis
title Nascent chain dynamics and ribosome interactions within folded ribosome-nascent chain complexes observed by NMR spectroscopy
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