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.
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