Elucidating the mechanisms underlying protein conformational switching using NMR spectroscopy

Abstract

How proteins switch between various ligand-free and ligand-bound structures has been a key biophysical question ever since the postulation of the Monod-Wyman-Changeux and Koshland-Nemethy-Filmer models over six decades ago. The ability of NMR spectroscopy to provide structural and kinetic information on biomolecular conformational exchange places it in a unique position as an analytical tool to interrogate the mechanisms of biological processes such as protein folding and biomolecular complex formation. In addition, recent methodological developments in the areas of saturation transfer and relaxation dispersion have expanded the scope of NMR for probing the mechanics of transitions in systems where one or more states constituting the exchange process are sparsely populated and 'invisible' in NMR spectra. In this review, we highlight some of the strategies available from NMR spectroscopy for examining the nature of multi-site conformational exchange, using five case studies that have employed NMR, either in isolation, or in conjunction with other biophysical tools.

Keywords

• Nuclear magnetic resonance
• Carr-Purcell-Meiboom-Gill relaxation dispersion
• Chemical exchange saturation transfer
• Conformational selection
• Induced fit
• Folding intermediates