Available online 12 September 2012
Publication year: 2012 Source:Archives of Biochemistry and Biophysics
NMR spectroscopy is one of the few biophysical methods that can provide atomic-level insight into the conformation of partially folded states and/or intermediates present along the protein folding pathway. Such studies are important not only within the context of the protein folding problem, but also to push forward the technique, due to the challenging nature of the systems studied. In fact, new NMR methods have been created, and applied, in an attempt to characterize the conformational features of the states along the folding pathway. Describing the structures along the folding landscape is of key importance to comprehend the folding reaction, design new proteins and to understand how several polypeptide chains are implicated in pathogenic amyloid states. The last advances in several approaches, which use NMR: (i) to monitor the protein folding pathway and/or, (ii) to characterize the structure of the intermediate states in such reaction are reviewed in this work. Graphical abstract
Highlights
? Structures of intermediates at atomic-resolution have been obtained by NMR. ? Intermediates have native-like topology. ? Intermediates have non-native contacts. ? The NMR view of folding agrees with that provided by other biophysical probes.
Measurement of protein unfolding/refolding kinetics and structural characterization of hidden intermediates by NMR relaxation dispersion [Biophysics and Computational Biology]
Measurement of protein unfolding/refolding kinetics and structural characterization of hidden intermediates by NMR relaxation dispersion
Meinhold, D. W., Wright, P. E....
Date: 2011-05-31
Detailed understanding of protein function and malfunction hinges on the ability to characterize transiently populated states and the transitions between them. Here, we use 15N, , and 13CO NMR R2 relaxation dispersion to investigate spontaneous unfolding and refolding events of native apomyoglobin. Above pH 5.0, dispersion is dominated by processes involving fluctuations of the F-helix region, which...
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Measurement of protein unfolding/refolding kinetics and structural characterization of hidden intermediates by NMR relaxation dispersion.
Measurement of protein unfolding/refolding kinetics and structural characterization of hidden intermediates by NMR relaxation dispersion.
Measurement of protein unfolding/refolding kinetics and structural characterization of hidden intermediates by NMR relaxation dispersion.
Proc Natl Acad Sci U S A. 2011 May 11;
Authors: Meinhold DW, Wright PE
Detailed understanding of protein function and malfunction hinges on the ability to characterize transiently populated states and the transitions between them. Here, we use (15)N, , and (13)CO NMR R(2)...
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05-13-2011 02:40 PM
[NMR paper] High-pressure NMR spectroscopy for characterizing folding intermediates and denatured
High-pressure NMR spectroscopy for characterizing folding intermediates and denatured states of proteins.
Related Articles High-pressure NMR spectroscopy for characterizing folding intermediates and denatured states of proteins.
Methods. 2004 Sep;34(1):133-43
Authors: Kamatari YO, Kitahara R, Yamada H, Yokoyama S, Akasaka K
Extensive structural studies using high-pressure NMR spectroscopy have recently been carried out on proteins, which potentially contribute to our understanding of the mechanisms of protein folding. Pressure shifts the...
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11-24-2010 10:01 PM
[NMR paper] Low-populated folding intermediates of Fyn SH3 characterized by relaxation dispersion
Low-populated folding intermediates of Fyn SH3 characterized by relaxation dispersion NMR.
Related Articles Low-populated folding intermediates of Fyn SH3 characterized by relaxation dispersion NMR.
Nature. 2004 Jul 29;430(6999):586-90
Authors: Korzhnev DM, Salvatella X, Vendruscolo M, Di Nardo AA, Davidson AR, Dobson CM, Kay LE
Many biochemical processes proceed through the formation of functionally significant intermediates. Although the identification and characterization of such species can provide vital clues about the mechanisms of the...
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[NMR paper] Use of selective Trp side chain labeling to characterize protein-protein and protein-
Use of selective Trp side chain labeling to characterize protein-protein and protein-ligand interactions by NMR spectroscopy.
Related Articles Use of selective Trp side chain labeling to characterize protein-protein and protein-ligand interactions by NMR spectroscopy.
J Am Chem Soc. 2003 Mar 12;125(10):2892-3
Authors: Rodriguez-Mias RA, Pellecchia M
Recent studies on amino acid occurrence in protein binding sites suggest that only a reduced number of residues are responsible for most interaction energy in protein-protein and protein-ligand...
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11-24-2010 09:01 PM
[NMR paper] Spin labels as a tool to identify and characterize protein-ligand interactions by NMR
Spin labels as a tool to identify and characterize protein-ligand interactions by NMR spectroscopy.
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Chembiochem. 2002 Mar 1;3(2-3):167-73
Authors: Jahnke W
NMR spectroscopy based discovery and optimization of lead compounds for a given molecular target requires the development of methods with maximum sensitivity and robustness. It is shown here that organic nitroxide radicals ("spin labels") can be used to boost the sensitivity...
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[NMR paper] Investigation of ribonuclease T1 folding intermediates by hydrogen-deuterium amide ex
Investigation of ribonuclease T1 folding intermediates by hydrogen-deuterium amide exchange-two-dimensional NMR spectroscopy.
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Biochemistry. 1993 Jun 22;32(24):6152-6
Authors: Mullins LS, Pace CN, Raushel FM
The rate of hydrogen bond formation at individual amino acid residues in ribonuclease T1 (RNase T1) has been investigated by the hydrogen-deuterium exchange-2D NMR (HDEx-2D NMR) technique (Udgaonkar...
NMR as a tool to identify and characterize protein folding intermediates
Highlights
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