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Protein Sci. 2019 Nov 13. doi: 10.1002/pro.3790. [Epub ahead of print]

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

Author information

1
Department of Medicinal Chemistry, University of Washington, Seattle, Washington.

Abstract

Much of our understanding of protein structure and mechanistic function has been derived from static high-resolution structures. As structural biology has continued to evolve it has become clear that high-resolution structures alone are unable to fully capture the mechanistic basis for protein structure and function in solution. Recently Hydrogen/Deuterium-exchange Mass Spectrometry (HDX-MS) has developed into a powerful and versatile tool for structural biologists that provides novel insights into protein structure and function. HDX-MS enables direct monitoring of a protein's structural fluctuations and conformational changes under native conditions in solution even as it is carrying out its functions. In this review, we focus on the use of HDX-MS to monitor these dynamic changes in proteins. We examine how HDX-MS has been applied to study protein structure and function in systems ranging from large, complex assemblies to intrinsically disordered proteins, and we discuss its use in probing conformational changes during protein folding and catalytic function. STATEMENT FOR A BROAD AUDIENCE: The biophysical and structural characterization of proteins provides novel insight into their functionalities. Protein motions, ranging from small scale local fluctuations to larger concerted structural rearrangements, often determine protein function. Hydrogen/Deuterium-exchange Mass Spectrometry (HDX-MS) has proven a powerful biophysical tool capable of probing changes in protein structure and dynamic protein motions that are often invisible to most other techniques.

KEYWORDS:

conformational switching; conformational transitions; hydrogen/deuterium-exchange mass spectrometry (HDX-MS); intrinsic disorder; structural dynamics; structural rearrangements

PMID:
31721348
DOI:
10.1002/pro.3790

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