Bridging protein structure, dynamics, and function using hydrogen/deuterium-exchange mass spectrometry

Area of Science:

• Structural Biology
• Biophysics
• Biochemistry

Background:

• Static high-resolution protein structures limit understanding of mechanistic function in solution.
• Protein dynamics and conformational changes are crucial for function but often missed by traditional methods.

Purpose of the Study:

• To review the application of Hydrogen/Deuterium-exchange Mass Spectrometry (HDX-MS) for monitoring dynamic protein changes.
• To highlight HDX-MS's utility in studying protein structure and function under native conditions.

Main Methods:

• Hydrogen/Deuterium-exchange Mass Spectrometry (HDX-MS) is presented as a key technique.
• HDX-MS allows direct monitoring of protein structural fluctuations and conformational dynamics in solution.

Main Results:

• HDX-MS provides novel insights into protein structure and function, complementing static structural data.
• The technique has been applied to diverse systems, including large assemblies and intrinsically disordered proteins.
• HDX-MS probes conformational changes during critical processes like protein folding and catalysis.

Conclusions:

• HDX-MS is a powerful tool for understanding protein dynamics and function in solution.
• It offers unique capabilities to observe dynamic events often invisible to other structural biology methods.
• This review underscores the value of HDX-MS in advancing the study of protein mechanics.