Zhuravleva, A and Korzhnev, DM (2017) Protein Folding by NMR. Progress in Nuclear Magnetic Resonance Spectroscopy, 100. pp. 52-77. ISSN 0079-6565
Abstract
Protein folding is a highly complex process proceeding through a number of disordered and partially folded nonnative states with various degrees of structural organization. These transiently and sparsely populated species on the protein folding energy landscape play crucial roles in driving folding toward the native conformation, yet some of these nonnative states may also serve as precursors for protein misfolding and aggregation associated with a range of devastating diseases, including neuro-degeneration, diabetes and cancer. Therefore, in vivo protein folding is often reshaped co- and post-translationally through interactions with the ribosome, molecular chaperones and/or other cellular components. Owing to developments in instrumentation and methodology, solution NMR spectroscopy has emerged as the central experimental approach for the detailed characterization of the complex protein folding processes in vitro and in vivo. NMR relaxation dispersion and saturation transfer methods provide the means for a detailed characterization of protein folding kinetics and thermodynamics under native-like conditions, as well as modeling high-resolution structures of weakly populated short-lived conformational states on the protein folding energy landscape. Continuing development of isotope labeling strategies and NMR methods to probe high molecular weight protein assemblies, along with advances of in-cell NMR, have recently allowed protein folding to be studied in the context of ribosome-nascent chain complexes and molecular chaperones, and even inside living cells. Here we review solution NMR approaches to investigate the protein folding energy landscape, and discuss selected applications of NMR methodology to studying protein folding in vitro and in vivo. Together, these examples highlight a vast potential of solution NMR in providing atomistic insights into molecular mechanisms of protein folding and homeostasis in health and disease.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Editors: |
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Copyright, Publisher and Additional Information: | © 2016, Elsevier. This is an author produced version of a paper published in Progress in Nuclear Magnetic Resonance Spectroscopy. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Nonnative protein states; folding intermediates; protein quality control; molecular chaperones; ribosome-nascent chain; in-cell NMR |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 14 Nov 2016 14:51 |
Last Modified: | 10 Nov 2018 01:38 |
Published Version: | https://doi.org/10.1016/j.pnmrs.2016.10.002 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.pnmrs.2016.10.002 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:107436 |