Developments in rapid hydrogen-deuterium exchange methods

• Published in: Essays in biochemistry Vol. 67; no. 2; p. 165
• Main Authors: Chow, Vimanda, Wolf, Esther, Lento, Cristina, Wilson, Derek J
• Format: Journal Article
• Language: English
• Published: England 29.03.2023
• Subjects: Deuterium; Deuterium Exchange Measurement - methods; Humans; Hydrogen - chemistry; Intrinsically Disordered Proteins - chemistry; Neurodegenerative Diseases; Protein Conformation; protein structure; hydrogen-deuterium exchange mass spectrometry; mass spectrometry; conformational dynamics; intrinsically disordered proteins
• ISSN: 1744-1358
• DOI: 10.1042/EBC20220174

Biological macromolecules, such as proteins, nucleic acids, and carbohydrates, contain heteroatom-bonded hydrogens that undergo exchange with solvent hydrogens on timescales ranging from microseconds to hours. In hydrogen-deuterium exchange mass spectrometry (HDX-MS), this exchange process is used to extract information about biomolecular structure and dynamics. This minireview focuses on millisecond timescale HDX-MS measurements, which, while less common than 'conventional' timescale (seconds to hours) HDX-MS, provide a unique window into weakly structured species, weak (or fast cycling) binding interactions, and subtle shifts in conformational dynamics. This includes intrinsically disordered proteins and regions (IDPs/IDRs) that are associated with cancer and amyloidotic neurodegenerative disease. For nucleic acids and carbohydrates, structures such as isomers, stems, and loops, can be elucidated and overall structural rigidity can be assessed. We will provide a brief overview of technical developments in rapid HDX followed by highlights of various applications, emphasising the importance of broadening the HDX timescale to improve throughput and to capture a wider range of function-relevant dynamic and structural shifts.