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Updated: Nov 23, 2025

Atomic Scale Structural Studies of Macromolecular Assemblies by Solid-state Nuclear Magnetic Resonance Spectroscopy
Published on: September 17, 2017
Dried Protein Structure Revealed at the Residue Level by Liquid-Observed Vapor Exchange NMR
Candice J Crilly1, Julia A Brom1, Mark E Kowalewski1
1Department of Chemistry, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-3290, United States.
Abstract:
Water is key to protein structure and stability, yet the relationship between protein-water interactions and structure is poorly understood, in part because there are few techniques that permit the study of dehydrated protein structure at high resolution. Here, we describe liquid-observed vapor exchange (LOVE) NMR, a solution NMR-based method that provides residue-level information about the structure of dehydrated proteins. Using the model protein GB1, we show that LOVE NMR measurements reflect the fraction of the dried protein population trapped in a conformation where a given residue is protected from exchange with D2O vapor. Comparisons to solution hydrogen-deuterium exchange data affirm that the dried protein structure is strongly influenced by local solution stability and that the mechanism of dehydration protection exerted by the widely used protectant trehalose differs from its mechanism of stabilization in solution. Our results highlight the need for refined models of cosolute-mediated dehydration protection and demonstrate the ability of LOVE NMR to inform such models.
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