Hydrogen-Deuterium Exchange Mass-Spectrometry of Secondary Active Transporters: From Structural Dynamics to Molecular Mechanisms

Frontiers in Pharmacology
Moshe Giladi, Daniel Khananshvili

Abstract

Membrane transporters allow the selective transport of otherwise poorly permeable solutes across the cell membrane and thus, play a key role in maintaining cellular homeostasis in all kingdoms of life. Importantly, these proteins also serve as important drug targets. Over the last decades, major progress in structural biology methods has elucidated important structure-function relationships in membrane transporters. However, structures obtained using methods such as X-ray crystallography and high-resolution cryogenic electron microscopy merely provide static snapshots of an intrinsically dynamic, multi-step transport process. Therefore, there is a growing need for developing new experimental approaches capable of exploiting the data obtained from the high-resolution snapshots in order to investigate the dynamic features of membrane proteins. Here, we present the basic principles of hydrogen-deuterium exchange mass-spectrometry (HDX-MS) and recent advancements in its use to study membrane transporters. In HDX-MS experiments, minute amounts of a protein sample can be used to investigate its structural dynamics under native conditions, without the need for chemical labelling and with practically no limit on the protein size. Thus,...Continue Reading

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Citations

Dec 29, 2020·Frontiers in Chemistry·Yousef BagheriMingxu You
May 1, 2021·International Journal of Molecular Sciences·Michał MarcinkowskiJarosław Poznański
May 2, 2021·Scientific Reports·Riley B PeacockElizabeth A Komives
May 9, 2021·Current Opinion in Structural Biology·Jani R BollaCarol V Robinson
Oct 29, 2020·Analytical Chemistry·John R EngenThomas E Wales

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Methods Mentioned

BETA
X-ray
electron microscopy
chemical exchange
reverse-phase chromatography

Software Mentioned

HDX
MS

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