Application of Hydrogen/Deuterium Exchange Mass Spectrometry in Structural Biology and Molecular Medicine

The diverse and expanding role of mass spectrometry in structural and molecular biology

The emergence of proteomics has led to major technological advances in mass spectrometry (MS). These advancements not only benefitted MS-based high-throughput proteomics but also increased the impact of mass spectrometry on the field of structural and molecular biology. Here, we review how state-of-the-art MS methods, including native MS, top-down protein sequencing, cross-linking-MS, and hydro...

On-tissue Direct Monitoring of Global Hydrogen/Deuterium Exchange by MALDI Mass Spectrometry: Tissue Deuterium Exchange Mass Spectrometry (TDXMS).

Hydrogen/deuterium exchange mass spectrometric (H/DXMS) methods for protein structural analysis are conventionally performed in solution. We present Tissue Deuterium Exchange Mass Spectrometry (TDXMS), a method to directly monitor deuterium uptake on tissue, as a means to better approximate the deuterium exchange behavior of proteins in their native microenvironment. Using this method, a differ...

Hydrogen/deuterium exchange mass spectrometry: potential for investigating innate immunity proteins.

Probing the non-covalent structure of proteins by amide hydrogen exchange and mass spectrometry.

The rates at which hydrogens located at peptide amide linkages in proteins undergo isotopic exchange when a protein is exposed to D2O depend on whether these amide hydrogens are hydrogen bonded and whether they are accessible to the aqueous solvent. Hence, amide hydrogen exchange rates are a sensitive probe for detecting changes in protein conformation and dynamics. Hydrogen exchange rates in p...

Dissection of conformational conversion events during prion amyloid fibril formation using hydrogen exchange and mass spectrometry.

A molecular understanding of prion diseases requires an understanding of the mechanism of amyloid fibril formation by the prion protein. In particular, it is necessary to define the sequence of the structural events describing the conformational conversion of monomeric PrP to aggregated PrP. In this study, the sequence of the structural events in the case of amyloid fibril formation by recombin...