Intrinsically Disordered Proteins Studied by NMR Spectroscopy

Bernhard Brutscher, Isabella C. Felli, Sergio Gil-Caballero, Tomáš Hošek, Rainer Kümmerle, Alessandro Piai, Roberta Pierattelli, Zsófia Sólyom, Brutscher, Bernhard, Felli, Isabella C., Gil-Caballero, Sergio, Hošek, Tomáš, Kümmerle, Rainer, Piai, Alessandro, Pierattelli, Roberta, Sólyom, Zsófia

Thanks to recent improvements in NMR instrumentation, pulse sequence design, and sample preparation, a panoply of new NMR tools has become available for atomic resolution characterization of intrinsically disordered proteins (IDPs) that are optimized for the particular chemical and spectroscopic properties of these molecules. A wide range of NMR observables can now be measured on increasingly complex IDPs that report on their structural and dynamic properties in isolation, as part of a larger complex, or even inside an entire living cell. Herein we present basic NMR concepts, as well as optimised tools available for the study of IDPs in solution. In particular, the following sections are discussed hereafter: a short introduction to NMR spectroscopy and instrumentation (Sect. 3.1), the effect of order and disorder on NMR observables (Sect. 3.2), particular challenges and bottlenecks for NMR studies of IDPs (Sect. 3.3), 2D HN and CON NMR experiments: the fingerprint of an IDP (Sect. 3.4), tools for overcoming major bottlenecks of IDP NMR studies (Sect. 3.5), (13)C detected experiments (Sect. 3.6), from 2D to 3D: from simple snapshots to site-resolved characterization of IDPs (Sect. 3.7), sequential NMR assignment: 3D experiments (Sect. 3.8), high-dimensional NMR experiments (nD, with n > 3) (Sect. 3.9) and conclusions and perspectives (Sect. 3.10).