Hofmeister Salts Recover a Misfolded Multiprotein Complex for Subsequent Structural Measurements in the Gas Phase

摘要

Proteins are the workhorses of the cell, the functions of which arc largely predicated on their structures and dynamics. Detailed knowledge of these attributes has enabled countless breakthroughs in human health and disease. Many aspects, however, of protein structure remain poorly understood, including their high-order interactions. This knowledge gap drives the development of new methods that are capable of protein structure characterization, some of which operate by measuring desolvated protein structure. Although desolvation enables the application of powerful analytical techniques that cannot be used in a solvated environment, and recent results indicate that many features of native protein structure survive in the gas phase, desolvation may also act to obfuscate critical details of protein conformation. Recently, multiple strategies have emerged for observing labile protein structures in the absence of bulk water and have proven useful in stabilizing protein-small-molecule interactions, globular proteins, and their complexes. Herein, we present the first evidence that a misfolded protein complex, which exists both in solution and in the gas phase, can be recovered back to a native-like structure by the addition of salts prior to desorption/ionization. This is the first time that such a solution-phase multiprotein folding equilibrium has been captured by gas-phase measurements.