Unraveling the dynamics of protein interactions with quantitative mass spectrometry

Abstract

Knowledge of structure and dynamics of proteins and protein complexes is important to unveil the molecular basis and mechanisms involved in most biological processes. Protein complex dynamics can be defined as the changes in the composition of a protein complex during a cellular process. Protein dynamics can be defined as conformational changes in a protein during enzyme activation, for example, when a protein binds to a ligand or when a protein binds to another protein. Mass spectrometry (MS) combined with affinity purification has become the analytical tool of choice for mapping protein–protein interaction networks and the recent developments in the quantitative proteomics field has made it possible to identify dynamically interacting proteins. Furthermore, hydrogen/deuterium exchange MS is emerging as a powerful technique to study structure and conformational dynamics of proteins or protein assemblies in solution. Methods have been developed and applied for the identification of transient and/or weak dynamic interaction partners and for the analysis of conformational dynamics of proteins or protein complexes. This review is an overview of existing and recent developments in studying the overall dynamics of in vivo protein interaction networks and protein complexes using MS-based methods.

Keywords::

• Quantitative proteomics
• protein interaction networks
• metabolic labeling
• label-free
• spectral counting
• H/D exchange

Acknowledgements

We would like to thank Dr. Mihaela Sardiu and Dr. Joshua M Gilmore for helpful discussions in preparation of the manuscript. This work was supported by the Stowers Institute for Medical Research.

Declaration of interest

The authors declare that they have no conflicts of interest.

Editor: Michael M. Cox