Structural mass spectrometry approaches to understand multidrug efflux systems
Structural mass spectrometry approaches to understand multidrug efflux systems
Multidrug efflux pumps are ubiquitous across both eukaryotes and prokaryotes, and have major implications in antimicrobial and multidrug resistance. They reside within cellular membranes and have proven difficult to study owing to their hydrophobic character and relationship with their compositionally complex lipid environment. Advances in structural mass spectrometry (MS) techniques have made it possible to study these systems to elucidate critical information on their structure–function relationships. For example, MS techniques can report on protein structural dynamics, stoichiometry, connectivity, solvent accessibility, and binding interactions with ligands, lipids, and other proteins. This information proving powerful when used in conjunction with complementary structural biology methods and molecular dynamics (MD) simulations. In the present review, aimed at those not experts in MS techniques, we report on the current uses of MS in studying multidrug efflux systems, practical considerations to consider, and the future direction of the field. In the first section, we highlight the importance of studying multidrug efflux proteins, and introduce a range of different MS techniques and explain what information they yield. In the second section, we review recent studies that have utilised MS techniques to study and characterise a range of different multidrug efflux systems.
255-267
Russell Lewis, Benjamin
6052ce96-6af8-4c50-a49c-594782e76493
Lawrence, Ryan
165dba3b-2b89-4e06-8d4d-2a3f889e8e70
Hammerschmid, Dietmar
5934e033-df57-4533-8e58-645ed0315759
Reading, Eamonn
62fed933-f867-4c72-89e7-83aea573a836
29 March 2023
Russell Lewis, Benjamin
6052ce96-6af8-4c50-a49c-594782e76493
Lawrence, Ryan
165dba3b-2b89-4e06-8d4d-2a3f889e8e70
Hammerschmid, Dietmar
5934e033-df57-4533-8e58-645ed0315759
Reading, Eamonn
62fed933-f867-4c72-89e7-83aea573a836
Russell Lewis, Benjamin, Lawrence, Ryan, Hammerschmid, Dietmar and Reading, Eamonn
(2023)
Structural mass spectrometry approaches to understand multidrug efflux systems.
Essays in Biochemistry, 67 (2), .
(doi:10.1042/ebc20220190).
Abstract
Multidrug efflux pumps are ubiquitous across both eukaryotes and prokaryotes, and have major implications in antimicrobial and multidrug resistance. They reside within cellular membranes and have proven difficult to study owing to their hydrophobic character and relationship with their compositionally complex lipid environment. Advances in structural mass spectrometry (MS) techniques have made it possible to study these systems to elucidate critical information on their structure–function relationships. For example, MS techniques can report on protein structural dynamics, stoichiometry, connectivity, solvent accessibility, and binding interactions with ligands, lipids, and other proteins. This information proving powerful when used in conjunction with complementary structural biology methods and molecular dynamics (MD) simulations. In the present review, aimed at those not experts in MS techniques, we report on the current uses of MS in studying multidrug efflux systems, practical considerations to consider, and the future direction of the field. In the first section, we highlight the importance of studying multidrug efflux proteins, and introduce a range of different MS techniques and explain what information they yield. In the second section, we review recent studies that have utilised MS techniques to study and characterise a range of different multidrug efflux systems.
Text
ebc-2022-0190c
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Accepted/In Press date: 23 November 2022
Published date: 29 March 2023
Additional Information:
Funding Information:
This work was supported by a UKRI Future Leaders Fellowship [grant number MR/S015426/1 (to E.R.)], a King’s College London studentship (to B.L.), and a BBSRC LiDo iCASE studentship with UCB Pharma [grant number BB/T008709/1 (to R.L.)].
Publisher Copyright:
© 2023 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).
Identifiers
Local EPrints ID: 478829
URI: http://eprints.soton.ac.uk/id/eprint/478829
ISSN: 1744-1358
PURE UUID: f329b238-42bf-4bcd-93a8-60aa1d81f781
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Date deposited: 11 Jul 2023 17:01
Last modified: 17 Mar 2024 04:19
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Author:
Benjamin Russell Lewis
Author:
Ryan Lawrence
Author:
Dietmar Hammerschmid
Author:
Eamonn Reading
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