Conformational Ensemble of Disordered Proteins Probed by Solvent Paramagnetic Relaxation Enhancement (sPRE). Issue 41 (12th September 2018)

• Record Type: Journal Article
• Authors: Kooshapur, Hamed; Schwieters, Charles D.; Tjandra, Nico
• Is Part Of: Angewandte Chemie international edition. Volume 57:Issue 41(2018)
• Page Start: 13519
• Page End: 13522
• Publication Date: 2018-09-12
• Subjects: ensemble calculations -- intrinsically disordered proteins -- NMR spectroscopy -- paramagnetic relaxation enhancement -- protein dynamics; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201807365
• Languages: English
• ISSNs: 1433-7851

Abstract

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. Abstract : Making sense out of disorder : An approach based on NMR paramagnetic relaxation enhancement from a soluble paramagnetic agent provides insights into the conformations of disordered proteins. Residues in the protein that form residual structures are less exposed to the solvent and give rise to low paramagnetic relaxation enhancements.