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Angew Chem Int Ed Engl. 2017 Jun 12;56(25):7070-7073. doi: 10.1002/anie.201700464. Epub 2017 May 16.

Real-Time Analysis of Folding upon Binding of a Disordered Protein by Using Dissolution DNP NMR Spectroscopy.

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Department of Biochemistry & Biophysics, Texas A&M University, College Station, TX, 77843, USA.
Department of Biochemistry and Molecular Biology, University of Florida College of Medicine, Gainesville, FL, 32611, USA.
Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
Department of Microbiology, Immunology and Biochemistry, The University of Tennessee Health Science Center, Memphis, TN, 38163, USA.
Department of Chemistry, Texas A&M University, College Station, TX, 77843, USA.


The kinase inhibitory domain of the cell cycle regulatory protein p27Kip1 (p27) was nuclear spin hyperpolarized using dissolution dynamic nuclear polarization (D-DNP). While intrinsically disordered in isolation, p27 adopts secondary structural motifs, including an α-helical structure, upon binding to cyclin-dependent kinase 2 (Cdk2)/cyclin A. The sensitivity gains obtained with hyperpolarization enable the real-time observation of 13 C NMR signals during p27 folding upon binding to Cdk2/cyclin A on a time scale of several seconds. Time-dependent intensity changes are dependent on the extent of folding and binding, as manifested in differential spin relaxation. The analysis of signal decay rates suggests the existence of a partially folded p27 intermediate during the timescale of the D-DNP NMR experiment.


NMR spectroscopy; hyperpolarization; intrinsically disordered proteins; protein folding; protein-protein interactions

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