Membrane proteins, such as receptors, transporters and ion channels, control the vast majority of cellular signalling and metabolite exchange processes and thus are becoming key pharmacological targets. Obtaining structural information by usage of traditional structural biology techniques is limited by the requirements for the protein samples to be highly pure and stable when handled in high concentrations and in non-native buffer systems, which is often difficult to achieve for membrane targets. Hence, there is a growing requirement for the use of hybrid, integrative approaches to study the dynamic and functional aspects of membrane proteins in physiologically relevant conditions. In recent years, significant progress has been made in the field of oxidative labelling techniques and in particular the X-ray radiolytic footprinting in combination with mass spectrometry (MS) (XF–MS), which provide residue-specific information on the solvent accessibility of proteins. In combination with both low- and high-resolution data from other structural biology approaches, it is capable of providing valuable insights into dynamics of membrane proteins, which have been difficult to obtain by other structural techniques, proving a highly complementary technique to address structure and function of membrane targets. XF–MS has demonstrated a unique capability for identification of structural waters and conformational changes in proteins at both a high degree of spatial and a high degree of temporal resolution. Here, we provide a perspective on the place of XF–MS among other structural biology methods and showcase some of the latest developments in its usage for studying water-mediated transmembrane (TM) signalling, ion transport and ligand-induced allosteric conformational changes in membrane proteins.
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October 2015
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Review Article|
October 09 2015
Oxidative footprinting in the study of structure and function of membrane proteins: current state and perspectives
Vassiliy N. Bavro;
Vassiliy N. Bavro
1
*Institute of Microbiology and Infection, School of Immunity and Infection, University of Birmingham, Birmingham B152TT, U.K.
1To whom correspondence should be addressed (emailv.bavro@bham.ac.uk).
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Sayan Gupta;
Sayan Gupta
†Center for Proteomics and Bioinformatics, Case Western Reserve University, Cleveland, OH 44106, U.S.A.
‡Berkeley Center for Structural Biology, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, U.S.A.
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Corie Ralston
Corie Ralston
‡Berkeley Center for Structural Biology, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, U.S.A.
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Publisher: Portland Press Ltd
Received:
May 29 2015
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2015 Authors; published by Portland Press Limited
2015
Biochem Soc Trans (2015) 43 (5): 983–994.
Article history
Received:
May 29 2015
Citation
Vassiliy N. Bavro, Sayan Gupta, Corie Ralston; Oxidative footprinting in the study of structure and function of membrane proteins: current state and perspectives. Biochem Soc Trans 1 October 2015; 43 (5): 983–994. doi: https://doi.org/10.1042/BST20150130
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