Application of NMR to studies of intrinsically disordered proteins

• Published in: Archives of biochemistry and biophysics 2017-08, Vol.628, p.57-70
• Main Authors: Gibbs, Eric B., Cook, Erik C., Showalter, Scott A.
• Format: Article
• Language: English
• Subjects: Amyloid; Amyloid - chemistry; Amyloid - metabolism; Animals; Humans; Intrinsically Disordered Proteins - chemistry; Intrinsically Disordered Proteins - metabolism; Isotope Labeling; Nuclear magnetic resonance; Nuclear Magnetic Resonance, Biomolecular - methods; Phase separation; Phosphorylation; Post-translational modification; Protein Processing, Post-Translational; Protein-protein interactions; Water - chemistry
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2017.05.008

The prevalence of intrinsically disordered protein regions, particularly in eukaryotic proteins, and their clear functional advantages for signaling and gene regulation have created an imperative for high-resolution structural and mechanistic studies. NMR spectroscopy has played a central role in enhancing not only our understanding of the intrinsically disordered native state, but also how that state contributes to biological function. While pathological functions associated with protein aggregation are well established, it has recently become clear that disordered regions also mediate functionally advantageous assembly into high-order structures that promote the formation of membrane-less sub-cellular compartments and even hydrogels. Across the range of functional assembly states accessed by disordered regions, post-translational modifications and regulatory macromolecular interactions, which can also be investigated by NMR spectroscopy, feature prominently. Here we will explore the many ways in which NMR has advanced our understanding of the physical-chemical phase space occupied by disordered protein regions and provide prospectus for the future role of NMR in this emerging and exciting field. [Display omitted] •Intrinsically disordered proteins are a focus in biophysics well-suited to NMR.•Site-specific knowledge of structure and post-translational modification is needed.•NMR is well-suited to investigate mechanistically important phase separation.•Solid-state NMR is especially well suited to study aggregation and amyloid states.•In-cell NMR provides for study of disordered proteins in a biological context.