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Angew Chem Int Ed Engl. 2018 Oct 8;57(41):13519-13522. doi: 10.1002/anie.201807365. Epub 2018 Sep 12.

Conformational Ensemble of Disordered Proteins Probed by Solvent Paramagnetic Relaxation Enhancement (sPRE).

Author information

1
Laboratory of Structural Biophysics, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
2
Office of Intramural Research, Center for Information Technology, National Institutes of Health, Bethesda, MD, 20892, USA.

Abstract

Characterization of the conformational ensemble of disordered proteins is highly important for understanding protein folding and aggregation mechanisms, but remains a computational and experimental challenge owing to the dynamic nature of these proteins. New observables that can provide unique insights into transient residual structures in disordered proteins are needed. Here using denatured ubiquitin as a model system, NMR solvent paramagnetic relaxation enhancement (sPRE) measurements provide an accurate and highly sensitive probe for detecting low populations of residual structure in a disordered protein. Furthermore, a new ensemble calculation approach based on sPRE restraints in conjunction with residual dipolar couplings (RDCs) and small-angle X-ray scattering (SAXS) is used to define the conformational ensemble of disordered proteins at atomic resolution. The approach presented should be applicable to a wide range of dynamic macromolecules.

KEYWORDS:

NMR spectroscopy; ensemble calculations; intrinsically disordered proteins; paramagnetic relaxation enhancement; protein dynamics

PMID:
30125451
DOI:
10.1002/anie.201807365

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