Real-Time Analysis of Folding upon Binding of a Disordered Protein by Using Dissolution DNPNMR Spectroscopy. Academic Article

abstract

• 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 -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 CNMR 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.

authors

• Hilty, Christian

published proceedings

• Angew Chem Int Ed Engl

altmetric score

• 1.25

author list (cited authors)

• Ragavan, M., Iconaru, L. I., Park, C., Kriwacki, R. W., & Hilty, C.

citation count

• 27

publication date

• January 2017

publisher

• Wiley  Publisher

published in

• Angewandte Chemie International Edition  Journal

keywords

• Cyclin A
• Cyclin-Dependent Kinase Inhibitor P27
• Cyclin-dependent Kinase 2
• Hyperpolarization
• Intrinsically Disordered Proteins
• Magnetic Resonance Spectroscopy
• NMR Spectroscopy
• Protein Binding
• Protein Folding
• Protein Structure, Secondary
• Protein-protein Interactions
• Solubility
• Time Factors

Digital Object Identifier (DOI)

• 10.1002/anie.201700464

start page

• 7070

end page

• 7073

volume

• 56

issue

• 25

URL

• http://dx.doi.org/10.1002/anie.201700464