Investigation of Intrinsically Disordered Proteins through Exchange with Hyperpolarized Water

Hyperpolarized water can selectively enhance NMR signals of rapidly exchanging protons in osteopontin (OPN), a metastasis‐associated intrinsically disordered protein (IDP), at near‐physiological pH and temperature. The transfer of magnetization from hyperpolarized water is limited to solvent‐exposed residues and therefore selectively enhances signals in 1H‐15N correlation spectra. Binding to the polysaccharide heparin was found to induce the unfolding of preformed structural elements in OPN. A fair exchange: The study of intrinsically disordered proteins under physiological conditions is often impeded by weak and overlapping NMR signals. This bottle‐neck can be overcome by means of dissolution dynamic nuclear polarization (D‐DNP). Selective proton exchange between hyperpolarized water with solvent‐exposed amino acids in osteopontin, a metastasis‐associated protein, casts light on the binding of this IDP to heparin.