Structural mass spectrometry goes viral

Adv Virus Res. 2019;105:189-238. doi: 10.1016/bs.aivir.2019.07.003. Epub 2019 Aug 27.


Over the last 20 years, mass spectrometry (MS), with its ability to analyze small sample amounts with high speed and sensitivity, has more and more entered the field of structural virology, aiming to investigate the structure and dynamics of viral proteins as close to their native environment as possible. The use of non-perturbing labels in hydrogen-deuterium exchange MS allows for the analysis of interactions between viral proteins and host cell factors as well as their dynamic responses to the environment. Cross-linking MS, on the other hand, can analyze interactions in viral protein complexes and identify virus-host interactions in cells. Native MS allows transferring viral proteins, complexes and capsids into the gas phase and has broken boundaries to overcome size limitations, so that now even the analysis of intact virions is possible. Different MS approaches not only inform about size, stability, interactions and dynamics of virus assemblies, but also bridge the gap to other biophysical techniques, providing valuable constraints for integrative structural modeling of viral complex assemblies that are often inaccessible by single technique approaches. In this review, recent advances are highlighted, clearly showing that structural MS approaches in virology are moving towards systems biology and ever more experiments are performed on cellular level.

Keywords: Capsid assembly; Charge detection mass spectrometry (CDMS); Fast photochemical oxidation of proteins (FPOP); Gas-phase electrophoretic mobility analysis (GEMMA); Ion mobility (IM); Protein conformational dynamics; Structural virology.

MeSH terms

  • Capsid / chemistry*
  • Capsid / metabolism*
  • Macromolecular Substances / chemistry
  • Macromolecular Substances / metabolism
  • Mass Spectrometry / methods*
  • Protein Interaction Mapping / methods*
  • Viral Proteins / chemistry*
  • Viral Proteins / metabolism*


  • Macromolecular Substances
  • Viral Proteins