Conformational Propensities of Intrinsically Disordered Proteins from NMR Chemical Shifts

• Published in: Chemphyschem Vol. 14; no. 13; pp. 3034 - 3045
• Main Authors: Kragelj, Jaka, Ozenne, Valéry, Blackledge, Martin, Jensen, Malene Ringkjøbing
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 16.09.2013; WILEY‐VCH Verlag; Wiley Subscription Services, Inc; Wiley-VCH Verlag
• Subjects: Biochemistry, Molecular Biology; chemical shifts; conformational propensities; ensemble description; Intrinsically Disordered Proteins; Intrinsically Disordered Proteins - chemistry; Life Sciences; NMR; Nuclear magnetic resonance; Nuclear Magnetic Resonance, Biomolecular; Protein Conformation; Proteins; Structural Biology; NMR; conformational propensities; intrinsically disordered proteins; chemical shifts; ensemble description
• ISSN: 1439-4235; 1439-7641
• DOI: 10.1002/cphc.201300387

The realization that a protein can be fully functional even in the absence of a stable three‐dimensional structure has motivated a large number of studies describing the conformational behaviour of these proteins at atomic resolution. Here, we review recent advances in the determination of local structural propensities of intrinsically disordered proteins (IDPs) from experimental NMR chemical shifts. A mapping of the local structure in IDPs is of paramount importance in order to understand the molecular details of complex formation, in particular, for IDPs that fold upon binding or undergo structural transitions to pathological forms of the same protein. We discuss experimental strategies for the spectral assignment of IDPs, chemical shift prediction algorithms and the generation of representative structural ensembles of IDPs on the basis of chemical shifts. Additionally, we highlight the inherent degeneracies associated with the determination of IDP sub‐state populations from NMR chemical shifts alone. Understanding protein disorder: Over the last decade, classical structural biology has experienced a shift towards a more dynamic paradigm with the realization that a protein can be fully functional even in the absence of a stable, folded structure. In this review the recent advances in the determination of conformational propensities of intrinsically disordered proteins at atomic resolution from experimental NMR chemical shifts are presented.