Detecting water-protein chemical exchange in membrane-bound proteins/peptides by solid-state NMR spectroscopy

Abstract

Water plays an important role in many essential biological processes of membrane proteins in hydrated lipid environments. In general, the 1H polarization transfers between water molecules and site-specific protons in proteins can be classified as coherent (via dipolar spin diffusion) and incoherent (via chemical exchange and nuclear Overhauser effect) transfers. Solid-state NMR is the technique of choice for studying such water-protein interactions in membrane-bound proteins/peptides through the detection of 1H polarization transfers from water to the proteins. These polarization transfer mechanisms often exist simultaneously and are difficult to quantify individually. Here, we review water-protein polarization transfer techniques in solid-state NMR, with a focus on the recent progress for the direct detection of site-specific kinetic water-protein chemical exchange processes on the sub-millisecond time scale in membrane-bound proteins. The measurements of the pure chemical exchange kinetics provide a unique opportunity to understand the role that water plays in the structure-function relationships of membrane-bound species at the water-bilayer interface. In addition, the perspective of chemical exchange saturation transfer (CEST) experiments in membrane-bound proteins/peptides is further discussed.