Protein studies by high-pressure NMR

Abstract

High-pressure NMR spectroscopy is a method that allows NMR measurements of any target samples under variable pressure. When applied to proteins, the method extends the conformational space that NMR spectroscopy can handle, from the space limited to the basic folded paradigm into the extensive conformational space that spans the entire high-energy paradigm of protein structure from the folded to the unfolded. The success of the experiment is ensured by the strong coupling between the volume and the conformation of a protein such that the partial molar volume of a protein decreases in parallel with the loss of its conformational order (the "volume theorem of protein") as advocated by Akasaka). The validity of this principle arises from the fact that a globular protein generally has a significant vacant space (sometimes called "void" or "cavities") inside its folded architecture into which water molecules may penetrate to reduce its partial molar volume and its conformational order simultaneously. Thanks to this principle, pressure provides a simple, clean, systematic and often efficient means of investigating the high-energy conformers of a protein, which is essential for understanding its folding, function, interaction, fibrillation, adaptation and evolution.