Visualizing transient dark states by NMR spectroscopy

Myriad biological processes proceed through states that defy characterization by conventional atomic-resolution structural biological methods. The invisibility of these ‘dark’ states can arise from their transient nature, low equilibrium population, large molecular weight, and/or heterogeneity. Alth...

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Bibliographic Details
Published in:Quarterly reviews of biophysics 2015-02, Vol.48 (1), p.35-116
Main Authors: Anthis, Nicholas J., Clore, G. Marius
Format: Article
Language:English
Subjects:
Atomic clocks
Biological
Biology
Dispersions
Encounters
Exchange
Heterogeneity
Magnetic Phenomena
Magnetic Resonance Spectroscopy - methods
NMR
Nuclear magnetic resonance
Proteins
Saturation
Spectrum analysis
Time Factors
Visibility
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Summary:Myriad biological processes proceed through states that defy characterization by conventional atomic-resolution structural biological methods. The invisibility of these ‘dark’ states can arise from their transient nature, low equilibrium population, large molecular weight, and/or heterogeneity. Although they are invisible, these dark states underlie a range of processes, acting as encounter complexes between proteins and as intermediates in protein folding and aggregation. New methods have made these states accessible to high-resolution analysis by nuclear magnetic resonance (NMR) spectroscopy, as long as the dark state is in dynamic equilibrium with an NMR-visible species. These methods – paramagnetic NMR, relaxation dispersion, saturation transfer, lifetime line broadening, and hydrogen exchange – allow the exploration of otherwise invisible states in exchange with a visible species over a range of timescales, each taking advantage of some unique property of the dark state to amplify its effect on a particular NMR observable. In this review, we introduce these methods and explore two specific techniques – paramagnetic relaxation enhancement and dark state exchange saturation transfer – in greater detail.
ISSN:0033-5835
1469-8994
1469-8994
DOI:10.1017/S0033583514000122