Elucidating binding mechanisms and dynamics of intrinsically disordered protein complexes using NMR spectroscopy

• Published in: Current opinion in structural biology Vol. 54; pp. 10 - 18
• Main Authors: Schneider, Robert, Blackledge, Martin, Jensen, Malene Ringkjøbing
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2019; Elsevier
• Subjects: Animals; Biochemistry, Molecular Biology; Humans; Intrinsically Disordered Proteins - chemistry; Intrinsically Disordered Proteins - metabolism; Life Sciences; Nuclear Magnetic Resonance, Biomolecular; Phosphorylation; Protein Binding; Protein Folding; Structural Biology
• ISSN: 0959-440X; 1879-033X
• DOI: 10.1016/j.sbi.2018.09.007

[Display omitted] •Intrinsically disordered proteins (IDPs) employ a variety of binding mechanisms.•They may form stable folded complex structures or remain highly dynamic.•Binding mechanisms, complex structures and dynamics can be studied by NMR spectroscopy.•We review progress in the field and highlight exemplary NMR studies of IDP complexes. Advances in characterizing complexes of intrinsically disordered proteins (IDPs) have led to the discovery of a remarkably diverse interaction landscape that includes folding-upon-binding, highly dynamic complexes, multivalent interactions as well as regulatory switches controlled by post-translational modifications. Nuclear magnetic resonance (NMR) spectroscopy has in recent years made significant contributions to this field by describing the binding mechanisms and mapping conformational dynamics on multiple time scales. Importantly, this progress has been associated with specific methodological developments in NMR, for example in exchange techniques, allowing challenging biological systems to be studied at atomic resolution. In general, the level of dynamics observed in IDP complexes does not correlate with binding affinities, demonstrating the intricate relationship between conformational dynamics and IDP regulatory function.