Issue 39, 2021

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

Abstract

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.

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

Supplementary files

Article information

Article type
Edge Article
Submitted
05 Aug 2021
Accepted
09 Sep 2021
First published
09 Sep 2021
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2021,12, 13120-13126

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

C. Burridge, C. A. Waudby, T. Włodarski, A. M. E. Cassaignau, L. D. Cabrita and J. Christodoulou, Chem. Sci., 2021, 12, 13120 DOI: 10.1039/D1SC04313G

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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