HDx-MS technology now available at MASSPROT (De Duve Institute)

With the acquisition of a new instrument dedicated to deuterium-hydrogen exchange, funded by the Fondation Contre le Cancer, the MASSPROT mass spectrometry platform is moving towards the study of protein structure.

This technique (HDx-MS) uses the ability of hydrogen atoms in the amino acids that form proteins (and other molecules) to exchange with deuterium ions present in solution.
As the speed of this exchange depends on the accessibility of each amino acid within a protein, this technique makes it possible not only to study the structure of proteins but also the sites of interaction between a protein and a ligand (another protein, small molecule, lipid, DNA, etc.) and to determine how pathological mutations modify the structure ('shape') of proteins.

Recently, the HDx-MS technique has made it possible to determine how a mutated protein in a type of blood cancer causes the disease by adopting a new 'shape' and interacting specifically with a receptor on the cell surface.
This finding, published in Nature Communications¹, also paves the way for the rational design of inhibitors of this interaction, inhibitors that could one day enable the disease to be cured.

Illustration of the HDx-MS technique

To study the accessibility of amino acids within a protein, the protein is dissolved in a solvent containing deuterium ions.
After a certain exchange time, the reaction is stopped and the protein is split into small pieces (peptides).
The identity of these peptides is determined by mass spectrometry, and the difference in mass between hydrogen (1 Da) and deuterium (2 Da) is used to determine which amino acids have incorporated deuterium and are therefore accessible to the solvent.