Hydrogen/Deuterium Exchange Mass Spectrometry - A Fourth Dimension in Structural Virology?

Abstract

Combatting viral diseases starts with a solid understanding of the viruses. Protein structures are an important part of this, as these structures are often highly correlated with protein function. Mass spectrometry can be employed to aid in the elucidation of these protein structures. This review will take a look in recent studies using hydrogen/deuterium exchange mass spectrometry (HDX-MS) in the context of structural virology. HDX-MS is a technique that can measure the amount of deuterium uptake in viral roteins under different conditions. Deuteration rates are heavily dependent on the environment of the residue, as reduction of solvent exposure and involvement in hydrogen bonding are key factors in the reduction of deuteration. This review will give examples of studies in which HDX-MS helped with the discovery of binding sites, protein conformations and allosteric effects of binding. Among others, HDX-MS helped in better understanding Influenza hemagglutinin activation, mapping of antibody epitopes on several viruses and better understanding allosteric effects in viral proteins. It will also give an overview of the general HDX-MS workflow and provide strengths and weaknesses of HDX-MS.